{"gene":"NDEL1","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2000,"finding":"NUDEL (NDEL1) was identified as a novel LIS1-interacting protein and a substrate of Cdk5 kinase. NUDEL is enriched at centrosomes and neuronal growth cones and interacts with cytoplasmic dynein. Inhibition of Cdk5 modifies NUDEL distribution in neurons and affects neuritic morphology.","method":"Co-immunoprecipitation, subcellular fractionation, in vitro kinase assay, immunofluorescence","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, direct kinase substrate assay, replicated across multiple methods in a focused study","pmids":["11163260"],"is_preprint":false},{"year":2003,"finding":"14-3-3epsilon binds to CDK5/p35-phosphorylated NUDEL and this binding maintains NUDEL phosphorylation. Deficiency of 14-3-3epsilon results in mislocalization of NUDEL and LIS1, consistent with reduction of cytoplasmic dynein function.","method":"Co-immunoprecipitation, genetic mouse models (Ywhae knockout/heterozygous), immunolocalization","journal":"Nature genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (Co-IP, mouse genetics, immunolocalization), replicated in vivo","pmids":["12796778"],"is_preprint":false},{"year":2002,"finding":"DISC1 interacts with NUDEL (NDEL1) via yeast two-hybrid, and the disease-associated truncation mutant of DISC1 fails to bind NUDEL. Expression of mutant DISC1 in PC12 cells reduces neurite extension.","method":"Yeast two-hybrid, co-immunoprecipitation, neurite outgrowth assay in PC12 cells","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — replicated across multiple studies with two orthogonal binding assays plus functional readout","pmids":["12506198"],"is_preprint":false},{"year":2003,"finding":"DISC1 interacts with NUDEL through a central coiled-coil domain of DISC1 that binds the C-terminal domain of NUDEL, independent from the LIS1 binding site on NUDEL. NUDEL acts as a bridge between DISC1 and LIS1, allowing formation of a trimolecular complex.","method":"Yeast two-hybrid, mammalian two-hybrid, co-immunoprecipitation, deletion mapping","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple binding assays across independent studies with domain mapping","pmids":["12812986","14962739"],"is_preprint":false},{"year":2004,"finding":"Ndel1 positively regulates dynein activity by facilitating the interaction between LIS1 and dynein. Loss of Ndel1 in developing neocortex impairs neuronal positioning and causes uncoupling of the centrosome and nucleus. Overexpression of LIS1 partially rescues the positioning defect caused by Ndel1 RNAi, placing Ndel1 upstream of dynein and in common pathway with LIS1.","method":"RNA interference in developing neocortex (in utero), epistasis rescue experiments, immunofluorescence","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis with rescue experiments, multiple orthogonal approaches, in vivo","pmids":["15473966"],"is_preprint":false},{"year":2003,"finding":"Nudel (NDEL1) is specifically phosphorylated in M phase by Cdc2 (CDK1) and by Erk1/2. Phosphorylation regulates its cell-cycle-dependent distribution and increases its association with Lis1. A Nudel mutant incapable of binding Lis1 impaired poleward movement of dynein and dynein-mediated transport of kinetochore proteins to spindle poles.","method":"In vitro kinase assays, phosphorylation-mimicking and phosphorylation-deficient mutants, immunofluorescence, functional mitosis assays","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — in vitro kinase assay, mutagenesis, functional readout in M phase, single lab","pmids":["12556484"],"is_preprint":false},{"year":2005,"finding":"Complete loss of Ndel1 results in embryonic lethality at the peri-implantation stage and cell proliferation defects. Compound heterozygous mice show neuronal migration defects. Ndel1 loss leads to abnormalities in microtubule organization and similar defects in dynein-dependent vesicle distribution as Lis1 loss. Rescue by LIS1, NDEL1, or NDE1 overexpression confirms they act in a common pathway.","method":"Targeted gene disruption (mouse knockout/hypomorph), MEF and granule cell assays, immunofluorescence, rescue experiments","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO mouse, epistasis rescue, multiple cell types and readouts","pmids":["16107726"],"is_preprint":false},{"year":2005,"finding":"CDK5-mediated phosphorylation of NDEL1 facilitates interaction between NDEL1 and katanin p60, and phosphorylated NDEL1 regulates the distribution of katanin p60. Loss of NDEL1 causes abnormal accumulation of p60 in nucleus. Loss of NDEL1 or dominant negative p60 in migrating neurons causes defective migration and elongation of nuclear-centrosomal distance.","method":"Co-immunoprecipitation, phosphorylation assays, dominant-negative expression, neuronal migration assay","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 / Moderate — co-IP, in vivo migration assay, phosphorylation-function link, single lab multiple methods","pmids":["16203747"],"is_preprint":false},{"year":2006,"finding":"Aurora-A phosphorylates NDEL1 at Ser251 at mitotic entry. This phosphorylation is required for centrosomal maturation and separation. NDEL1 is required for centrosome targeting of TACC3 through direct interaction with TACC3. Aurora-A phosphorylation-mimetic NDEL1 mutants rescue centrosomal maturation/separation defects in Aurora-A-depleted cells.","method":"In vitro kinase assay, phosphomimetic/phosphodeficient mutants, siRNA depletion rescue, immunofluorescence, co-immunoprecipitation","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — in vitro kinase assay, mutagenesis rescue, co-IP for TACC3 interaction, single lab","pmids":["17060449"],"is_preprint":false},{"year":2007,"finding":"DISC1 directly interacts with kinesin-1 heavy chain and links the NUDEL/LIS1/14-3-3epsilon complex to kinesin-1 for anterograde axonal transport. Knockdown of DISC1 inhibited accumulation of NUDEL, LIS1, and 14-3-3epsilon at axons and inhibited axon elongation.","method":"Co-immunoprecipitation, RNAi knockdown, immunofluorescence, axon elongation assay","journal":"The Journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, RNAi with functional readout, single lab","pmids":["17202468"],"is_preprint":false},{"year":2007,"finding":"Cenp-F interacts with Ndel1 and Nde1, and Ndel1/Nde1/Lis1 localize to kinetochores in a Cenp-F-dependent manner. Inhibition of Ndel1 leads to chromosome malalignments not detected by the spindle checkpoint, resulting in lagging chromosomes during anaphase. Ndel1 and Nde1 play distinct roles at kinetochores.","method":"Co-immunoprecipitation, siRNA knockdown, live cell imaging, immunofluorescence","journal":"Current biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — Co-IP, RNAi with defined cellular phenotype, functional distinction between Ndel1 and Nde1, multiple orthogonal methods","pmids":["17600710"],"is_preprint":false},{"year":2007,"finding":"Ndel1 is required for robust localization of dynein/dynactin at the kinetochore. Kinetochore localization of Nudel depends mostly (~78%) on mitosin (CENP-F) and slightly on dynein/dynactin. Nudel activates dynein-mediated protein transport at the kinetochore and stabilizes kinetochore dynein/dynactin against microtubule-dependent stripping.","method":"RNAi, mutant overexpression, time-lapse imaging, immunofluorescence","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi with defined kinetochore phenotype, mutant analysis, single lab","pmids":["17494871"],"is_preprint":false},{"year":2007,"finding":"Crystal structure of two fragments of the coiled-coil domain of Ndel1 (residues 10-166) revealed a stable parallel homodimer with supercoiled alpha helices. The structure suggests how the Lis1-interacting domain can be regulated via cooperative binding of two Ndel1 helices to a Lis1 homodimer.","method":"X-ray crystallography, solution studies (solution NMR/biophysics)","journal":"Structure","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure with complementary solution studies, single study","pmids":["17997972"],"is_preprint":false},{"year":2004,"finding":"NUDEL directly interacts with neurofilament light subunit (NF-L) and facilitates the polymerization of neurofilaments. Knockdown of NUDEL by RNAi destabilizes NF-L and alters neurofilament homeostasis, resulting in morphological changes reminiscent of neurodegeneration.","method":"Co-immunoprecipitation, RNAi knockdown in neuroblastoma cells and primary cortical neurons, in vitro polymerization assay","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — direct interaction assay, in vitro polymerization assay, RNAi in multiple systems, single lab","pmids":["15208636"],"is_preprint":false},{"year":2004,"finding":"Nudel (NDEL1) regulates dynein-mediated membrane transport through direct interactions with both Lis1 and dynein heavy chain. A Nudel mutant defective in Lis1 or dynein heavy chain binding causes dispersion of dynein-dependent membranous organelles and reduces frequency and velocity of lysosome minus-end-directed motions.","method":"Mutant overexpression, RNAi, time-lapse microscopy for lysosome motility, organelle localization assays","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — structure-function mutants, time-lapse imaging with quantitative motility analysis, single lab","pmids":["14970193"],"is_preprint":false},{"year":2005,"finding":"Nudel (Ndl1 in budding yeast) targets dynein to microtubule plus ends through LIS1. The Ndl1 null mutant shows decreased targeting of dynein to microtubule plus ends. Ndl1 regulates dynein targeting through LIS1 but not through CLIP170.","method":"Yeast genetics (null mutant), live cell imaging, biochemical interaction assays","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic null in yeast ortholog, live imaging, biochemical confirmation, multiple approaches","pmids":["15965467"],"is_preprint":false},{"year":2005,"finding":"Nudel (NDEL1) contributes to microtubule anchoring at the mother centriole. Nudel localizes to mother centriole and its centrosome localization requires a C-terminal region essential for associations with dynein, dynactin, PCM-1, pericentrin, and gamma-tubulin. Nudel plays roles in both dynein-mediated transport of dynactin/Lis1/PCM-1 and dynein-independent centrosomal targeting of pericentrin and gamma-tubulin.","method":"RNAi, mutant overexpression, immunofluorescence, co-immunoprecipitation","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi with defined phenotype, mutant mapping, co-IP, single lab","pmids":["16291865"],"is_preprint":false},{"year":2008,"finding":"LIS1 suppresses the motility of cytoplasmic dynein on microtubules, while NDEL1 releases the blocking effect of LIS1 on cytoplasmic dynein. LIS1 mediates anterograde transport of cytoplasmic dynein as a dynein-LIS1 complex on transportable microtubule fragments.","method":"In vitro microtubule motility assay, blocking antibody experiments, co-immunoprecipitation","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro motility reconstitution, antibody blocking, Co-IP, single lab","pmids":["18784752"],"is_preprint":false},{"year":2008,"finding":"Protein phosphatase 4 catalytic subunit (PP4c) dephosphorylates NDEL1 at CDK1 sites. Loss of PP4c leads to unscheduled CDK1 activation and abnormal NDEL1 phosphorylation, which causes excessive recruitment of katanin p60 to the centrosome and microtubule disorganization. Inhibition of CDK1, NDEL1, or katanin p60 rescues the defects caused by PP4 inhibition.","method":"In vitro phosphatase assay, targeted gene disruption, pharmacological CDK1 inhibition, epistasis rescue","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — in vitro phosphatase assay, genetic KO, pharmacological epistasis, multiple orthogonal methods","pmids":["18347064"],"is_preprint":false},{"year":2008,"finding":"Lis1 and Ndel1 reduction impairs prophase nuclear envelope invagination (PNEI), a dynein-dependent process facilitating nuclear envelope breakdown (NEBD). Ndel1 phosphorylation is important for this function, regulating binding to both Lis1 and dynein.","method":"siRNA knockdown, live cell imaging, phosphomimetic/phosphodeficient mutants, mouse brain histology","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA with live imaging, mutagenesis, in vivo validation, single lab","pmids":["18809722"],"is_preprint":false},{"year":2008,"finding":"Nudel interacts with Cdc42GAP and competes with Cdc42 for binding Cdc42GAP, inhibiting Cdc42GAP-mediated inactivation of Cdc42 in a dose-dependent manner. Nudel's leading-edge localization in migrating cells requires phosphorylation by Erk1/2. Depleting Nudel or expressing a non-phosphorylatable mutant abolishes Cdc42 activation and cell migration.","method":"Co-immunoprecipitation, competitive binding assay, RNAi, phosphomimetic mutants, Cdc42 activation assay, migration assay","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 / Moderate — competitive binding assay, RNAi with functional readout, Erk phosphorylation-localization link, multiple approaches single lab","pmids":["18331715"],"is_preprint":false},{"year":2008,"finding":"Ndel1 forms a novel complex with vimentin, dynein, Lis1, and alphaCOP. Ndel1 promotes interaction between Lis1, alphaCOP, and the vimentin-dynein complex, activating dynein-mediated transport of vimentin. Loss of Ndel1 by RNAi fails to incorporate Lis1/alphaCOP in the complex, reduces vimentin transport, and alters neuritogenesis.","method":"Tandem affinity purification, co-immunoprecipitation, RNAi, transport assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — TAP-MS identification, co-IP validation, RNAi with functional readout, single lab","pmids":["18303022"],"is_preprint":false},{"year":2009,"finding":"aPKC phosphorylates Aurora A at Thr287, which facilitates Aurora A interaction with TPX2 and activates Aurora A at the neurite hillock, leading to phosphorylation of NDEL1 at S251 and NDEL1 recruitment. Suppression of aPKC, Aurora A, TPX2, or Ndel1 impairs neurite extension. Suppression of this pathway decreases frequency of microtubule emanation from the MTOC.","method":"In vitro kinase assays, RNAi, phosphomimetic mutants, live microtubule plus-end marker imaging, immunofluorescence","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — in vitro kinase assay, live imaging of MT dynamics, RNAi pathway placement, multiple methods single lab","pmids":["19668197"],"is_preprint":false},{"year":2009,"finding":"Palmitoylation of Ndel1 by specific palmitoylation enzymes occurs in vivo. Unpalmitoylated Ndel1 interacts better with dynein; palmitoylated Ndel1 reduces cytoplasmic dynein activity, as shown by Golgi distribution, vesicle trafficking, retrograde transport of dynein, and neuronal migration assays.","method":"Palmitoylation assay (metabolic labeling), co-immunoprecipitation, organelle localization assays, neuronal migration assay, time-lapse imaging","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct palmitoylation detection, multiple functional readouts, mechanistic link between modification and dynein binding, single lab","pmids":["19927128"],"is_preprint":false},{"year":2009,"finding":"Nudel binds to paxillin at nascent adhesions and colocalization is observed in areas of active membrane protrusions. Focal adhesion kinase (FAK) disrupts the Nudel-paxillin interaction in a paxillin-binding-dependent manner. Forced localization of Nudel to all focal contacts markedly strengthened adhesivity, while overexpression of activated FAK caused cell edge shrinkage.","method":"Co-immunoprecipitation, fusion protein forced localization, RNAi, cell migration assays, immunofluorescence","journal":"PLoS biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, structure-function analysis, functional migration/adhesion assays, single lab","pmids":["19492042"],"is_preprint":false},{"year":2009,"finding":"Nudel is required for retrograde axonal transport in DRG neurons; anti-Nudel antibody injection abolishes retrograde transport of membranous organelles and leads to lysosome accumulation in axons and delayed endo-lysosome formation.","method":"Microinjection of blocking antibody into cultured DRG neurons, time-lapse microscopy, Golgi and lysosome localization assays","journal":"Traffic","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct antibody perturbation in neurons, time-lapse imaging, defined phenotypic readout, single lab","pmids":["19522757"],"is_preprint":false},{"year":2010,"finding":"Depletion of both NDE1 and NDEL1 causes striking dispersal of Golgi and endocytic organelles and complete loss of dynein from membranes. A substantial portion of NDE1 and NDEL1 is membrane-associated. NDE1 and NDEL1 act upstream of LIS1 in dynein recruitment on membrane: exogenous NDE1 or NDEL1 rescues LIS1 depletion effects on Golgi, while LIS1 only partially rescues loss of NDE1 and NDEL1.","method":"siRNA knockdown (single and double), organelle localization imaging, membrane fractionation, epistasis rescue experiments","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — double KD epistasis, fractionation, rescue experiments, single lab multiple methods","pmids":["20048338"],"is_preprint":false},{"year":2010,"finding":"Nudel/Ndel1 regulates microtubule organization during spindle assembly independently of kinetochore functions. Nudel directly interacts with lamin B to facilitate lamin-B-containing matrix accumulation and assembly on microtubules in a dynein-dependent manner. A novel dynein binding domain within the first 80 amino acids of Nudel was identified that interacts with dynein intermediate chain.","method":"Xenopus egg extract spindle assembly assay, immunodepletion, protein binding assays, extensive mutagenesis","journal":"Nature cell biology / The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — reconstitution in Xenopus extract, mutagenesis, biochemical binding assays, identifies specific domain","pmids":["19198602","21056974"],"is_preprint":false},{"year":2010,"finding":"Genetic mosaic analysis (MADM) established that Ndel1 is required cell-autonomously for a specific late step of neuronal migration: entry into the target lamina, distinct from Lis1's role in migration efficiency.","method":"Mosaic Analysis with Double Markers (MADM), in vivo sparse clonal analysis in mouse cortex","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 / Strong — rigorous in vivo genetic mosaic analysis, cell-autonomous function established at single-cell resolution","pmids":["21092859"],"is_preprint":false},{"year":2011,"finding":"Cdk5-phosphorylated Ndel1 promotes a high-affinity Lis1/Ndel1/dynein complex that blocks ATP-dependent release of dynein from microtubules, inhibiting processive motility. In adult axons, unphosphorylated Ndel1 inhibits dynein-mediated transport; Cdk5 phosphorylation of Ndel1 releases this inhibition and allows Lis1 to further stimulate cargo transport.","method":"RNAi, phosphorylation mutants, organelle transport assays in adult DRG axons, dominant-negative Cdk5","journal":"The Journal of neuroscience / Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple studies with phosphomimetics, RNAi, dominant negatives, consistent mechanistic conclusion","pmids":["22114287","26166569"],"is_preprint":false},{"year":2005,"finding":"NUDEL possesses endooligopeptidase (cysteine protease) activity; mutation of Cys-273 fully abolishes this activity without disrupting secondary structure. DISC1 inhibits NUDEL-oligopeptidase activity in a competitive fashion, and the catalytic site is close to the DISC1-binding site on NUDEL.","method":"Site-directed mutagenesis of catalytic Cys-273, enzymatic activity assay, competitive inhibition assay","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Moderate — active-site mutagenesis with enzymatic assay, competitive inhibition kinetics, single lab","pmids":["15728732"],"is_preprint":false},{"year":2010,"finding":"The endooligopeptidase activity of Ndel1 is functionally important for neurite outgrowth in PC12 cells. Wild-type Ndel1 increases neurite-bearing cells; the catalytically dead mutant Ndel1(C273A) decreases neurite outgrowth; and RNAi depletion of Ndel1 is rescued by enzymatically active Ndel1(WT) but not Ndel1(C273A).","method":"RNAi, rescue with wild-type vs. catalytic mutant, neurite outgrowth quantification in PC12 cells","journal":"Molecular and cellular neurosciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi rescue with catalytic mutant provides mechanistic specificity, single lab","pmids":["20462516"],"is_preprint":false},{"year":2008,"finding":"Ndel1 directly interacts with PDE4 family members, and the interaction with PDE4D3 is specifically disrupted by PKA phosphorylation at Ser13 of PDE4D3. Ndel1 sequesters EPAC (but not PKA) to form a cAMP signaling complex. Ndel1 self-interaction (dimerization) is stabilized by PDE4 binding.","method":"Co-immunoprecipitation, BRET interaction assay in living cells, peptide array mapping, PKA phosphorylation assay","journal":"Cellular signalling","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — BRET in living cells, Co-IP, peptide array, single lab with multiple methods","pmids":["18845247"],"is_preprint":false},{"year":2011,"finding":"PKA phosphorylates NDE1 at threonine-131 (T131) in a DISC1/PDE4-dependent manner. T131 phosphorylation modulates NDE1-LIS1 and NDE1-NDEL1 interactions, as confirmed by homology modeling and experimental binding assays. Mutation of T131 to mimic PKA phosphorylation inhibits neurite outgrowth.","method":"In vitro kinase assay, co-immunoprecipitation, homology modeling, neurite outgrowth assay, immunofluorescence","journal":"The Journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — kinase assay, binding assays, functional readout, but primarily focused on NDE1; NDEL1 interaction is a secondary finding","pmids":["21677187"],"is_preprint":false},{"year":2012,"finding":"Full-length NDEL1 forms dimers, tetramers, and chain-like polymers with a folded-back structure in solution. The C-terminal region, required for interaction with dynein and DISC1, folds back onto the N-terminal coiled-coil domain. NDE1 and NDEL1 can interact directly to form mixed complexes.","method":"Negative stain electron microscopy, chemical cross-linking/mass spectrometry, isotope labeling, biophysical characterization","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — structural EM, cross-linking MS, multiple biophysical methods, single study","pmids":["22843697"],"is_preprint":false},{"year":2012,"finding":"Nudel directly interacts with misfolded Gβ (mfGβ) and recruits it to cytoplasmic dynein for transport to the centrosome/aggresome. Depletion of Nudel by RNAi reduces dynein-associated mfGβ, impairs aggresome formation, and prolongs the half-life of nascent Gβ.","method":"Co-immunoprecipitation, RNAi, half-life measurement, aggresome formation assay","journal":"Cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, RNAi with defined functional readout (protein quality control), single lab","pmids":["22430153"],"is_preprint":false},{"year":2012,"finding":"Nudel is crucial for in vivo assembly of the WAVE regulatory complex (WRC). Nudel stabilizes the Sra1-Nap1-Abi1 subcomplex through dynamic binding to Sra1 and protects HSPC300 from proteasomal degradation, stimulating HSPC300-WAVE2 complex formation. Depletion of Nudel abolishes WRC-dependent actin polymerization in vitro and Rac1-induced lamellipodial actin networks.","method":"Co-immunoprecipitation, RNAi, in vitro actin polymerization assay, cell spreading assay","journal":"Cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro actin assay, RNAi, Co-IP for subcomplex interactions, single lab","pmids":["22453242"],"is_preprint":false},{"year":2013,"finding":"LIS1 is required for mitotic spindle organization via the LIS1-NDEL1-dynein complex. Overexpression of NDEL1-dynein and microtubule stabilization rescues spindle orientation defects in Lis1 mutants, placing NDEL1-dynein downstream of LIS1 in spindle orientation.","method":"Lis1 mutant mouse embryonic fibroblasts, time-lapse live cell imaging, rescue experiments, immunofluorescence","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic mutant, epistasis rescue, live imaging, single lab","pmids":["24030547"],"is_preprint":false},{"year":2013,"finding":"Ndel1 and NudCL together regulate retrograde axonal mitochondrial transport. Knocking down both Ndel1 and NudCL almost blocks retrograde mitochondrial transport, while each alone only partially reduces it. LIS1 also interacts with KIF5b (kinesin) and its depletion suppresses mitochondrial motility in both anterograde and retrograde directions.","method":"siRNA knockdown (single and double), live imaging of mitochondrial transport in hippocampal neurons, co-immunoprecipitation","journal":"Traffic","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — double KD epistasis, live imaging quantification, single lab","pmids":["23551859"],"is_preprint":false},{"year":2016,"finding":"NDEL1 localizes to the axon initial segment (AIS) via interaction with the scaffold protein Ankyrin-G. Depletion of NDEL1 or LIS1 results in non-polarized trafficking of dendritic cargo through the AIS. NDEL1 facilitates reversal of somatodendritic cargos in the proximal axon via local dynein activation.","method":"Co-immunoprecipitation, RNAi, live cargo tracking, immunofluorescence, fractionation","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 / Moderate — Co-IP, RNAi with live cargo tracking, defined localization mechanism, single lab multiple methods","pmids":["26844830"],"is_preprint":false},{"year":2016,"finding":"Ndel1 localizes to the subdistal appendage of the mother centriole and suppresses primary cilia formation in proliferating cells by maintaining trichoplein at the mother centriole, thereby sustaining Aurora A activation. Serum starvation induces transient Ndel1 degradation followed by trichoplein disappearance and cilia assembly. Ndel1 acts upstream of the trichoplein-Aurora A pathway.","method":"siRNA knockdown, forced expression, immunofluorescence, mouse genetics (Ndel1 hypomorphic mice), co-localization studies","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — epistasis via rescue experiments, in vivo mouse model, siRNA, multiple orthogonal approaches","pmids":["26880200"],"is_preprint":false},{"year":2016,"finding":"Ndel1 interacts with TRIO-associated repeat on actin (Tara), an actin-bundling protein. Loss of Ndel1 or Tara impairs cell migration. Tara overexpression induces accumulation of Ndel1 at the cell periphery co-localizing with F-actin. Co-expression of Ndel1 and Tara causes synergistic increase in F-actin and filopodia formation.","method":"Co-immunoprecipitation, RNAi, wound healing and Boyden chamber migration assays, immunofluorescence","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, RNAi with migration phenotype, synergy assay, single lab","pmids":["27546710"],"is_preprint":false},{"year":2017,"finding":"Crystal structure of DISC1 C-terminal tail in complex with Ndel1 binding domain was solved at high resolution. DISC1 regulates Ndel1 kinetochore attachment (but not centrosome localization) during mitosis. Disrupting DISC1/Ndel1 complex formation prolongs mitotic length and causes cell-cycle deficits in human cells and mouse cortical radial glia.","method":"X-ray crystallography, co-immunoprecipitation, live cell imaging, mouse in utero electroporation, human forebrain organoids, patient iPSCs","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure combined with functional validation in multiple systems (human cells, mouse, organoids, patient iPSCs)","pmids":["29103808"],"is_preprint":false},{"year":2019,"finding":"Crystal structure of AnkB in complex with Ndel1 C-terminal coiled-coil (CT-CC) region revealed a stable 5-helix bundle with 2:1 (Ndel1:AnkB) stoichiometry. AnkG is essential for Ndel1 accumulation at the AIS. Cargo sorting at the AIS is disrupted by a peptide designed to block the AnkG/Ndel1 complex.","method":"X-ray crystallography, co-immunoprecipitation, live cargo tracking, peptide competition assay","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure with functional validation (peptide disruption of cargo sorting), single lab","pmids":["31889000"],"is_preprint":false},{"year":2015,"finding":"GSK-3β phosphorylates dynein intermediate chain (IC) at conserved residues S87/T88 (IC-1B) and S88/T89 (IC-2C) within the Ndel1-binding domain. This phosphorylation reduces IC interaction with Ndel1. Pharmacological or genetic inhibition of GSK-3β stimulates dynein motility.","method":"Co-immunoprecipitation, mass spectrometry, site-directed mutagenesis, in vitro phosphorylation assay, dynein motility assay","journal":"Traffic","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — in vitro phosphorylation, MS identification, mutagenesis, functional motility assay, single lab","pmids":["26010407"],"is_preprint":false},{"year":2015,"finding":"DBZ (DISC1-binding zinc finger protein) hinders Ndel1 phosphorylation at Thr219 and Ser251. DBZ depletion or expression of double-phosphorylated Ndel1 impairs anterograde transport of Lis1 and DISC1 to neurite tips. This identifies a role for Ndel1 dual-phosphorylation state in regulating anterograde transport.","method":"RNAi, phosphomimetic expression, in utero electroporation, immunofluorescence, microtubule elongation assay","journal":"The Journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — phosphomimetic mutants, in vivo electroporation, rescue experiments, single lab","pmids":["25698733"],"is_preprint":false},{"year":2017,"finding":"NDEL1 is specifically S-nitrosylated at Cys203 by neuronal nitric oxide synthase (nNOS) in an NMDA receptor-activity-dependent manner. This S-nitrosylation accelerates dendritic arborization. Disruption of NDEL1 S-nitrosylation mediates impaired dendritic maturation caused by developmental alcohol exposure.","method":"Biotin-switch S-nitrosylation assay, site-directed mutagenesis of Cys203, genetic Nos1 deletion, NMDA receptor pharmacology, dendritic morphometry","journal":"Cerebral cortex","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct S-nitrosylation assay with site-specific mutant, genetic NOS1 KO, functional dendritic readout, single lab","pmids":["27371763"],"is_preprint":false},{"year":2011,"finding":"Ndel1 directly associates with Dynamin 2 (Dyn2) and enhances Dyn2 GTPase activity in its unassembled and assembled forms without promoting oligomerization. Gain and loss of function of Ndel1 recapitulate effects of Dyn2 overexpression or dominant-negative Dyn2 on intracellular localization of GluR1.","method":"Co-immunoprecipitation, in vitro GTPase activity assay, gain/loss-of-function experiments, GluR1 localization assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — in vitro GTPase assay, co-IP, gain/loss of function, single lab","pmids":["21283621"],"is_preprint":false},{"year":2021,"finding":"Ndel1 binds directly to keratin subunits through a motif conserved in all intermediate filament proteins and is necessary for robust desmosome-keratin association. Lis1 is required for desmosomal localization of Ndel1 but not for its effects on keratin filaments. Loss of Ndel1 in mouse epidermis results in desmosome defects.","method":"Direct binding assay, mouse genetics (conditional KO), immunofluorescence, desmosome morphology analysis","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding assay, mouse genetic KO with defined phenotype, mechanistic dissection of Lis1 role, single lab","pmids":["34319758"],"is_preprint":false},{"year":2023,"finding":"The dynein intermediate chain N-terminus (ICN) is a critical evolutionarily conserved hub that interacts with both dynactin and Ndel1. Ndel1 recruits LIS1 to the dynein complex via ICN binding. LIS1 cannot simultaneously bind Ndel1 and dynein, requiring LIS1 to be handed off from Ndel1 to dynein in temporally discrete steps. In vitro, Ndel1 inhibits dynein activation by disfavoring dynein-dynactin-adaptor complex formation and by sequestering Lis1 away from dynein. Phosphomimetic C-terminal domain mutations in Ndel1 increase its ability to inhibit dynein-dynactin-adaptor complex formation.","method":"Purified protein binding assays, single-molecule imaging, in vitro reconstitution of dynein-dynactin-adaptor complex, mutagenesis","journal":"Nature communications / The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with purified components, single-molecule imaging, mutagenesis, replicated across two independent publications","pmids":["37730751","37086789"],"is_preprint":false},{"year":2024,"finding":"The NDEL1 variant p.R105P disrupts NDEL1 binding to LIS1, impairs neuronal migration, increases leading process length, and disrupts nucleus-centrosome coupling (nucleokinesis). This identifies the critical role of the LIS1-binding interface of NDEL1 in nucleokinesis during cortical development.","method":"In utero electroporation (mouse), single-cell RNA sequencing, spatial transcriptomics, biochemical binding assay, patient variant analysis","journal":"Acta neuropathologica","confidence":"High","confidence_rationale":"Tier 2 / Moderate — disease variant functional validation in vivo, biochemical binding disruption, multiple orthogonal methods, single study","pmids":["38194050"],"is_preprint":false}],"current_model":"NDEL1 is a multifunctional scaffold protein that directly binds LIS1, cytoplasmic dynein intermediate chain, and dynactin to regulate dynein activation; it recruits LIS1 to dynein through the intermediate chain N-terminus and must be released before LIS1 is handed off to dynein for processive transport. NDEL1 activity is regulated by multiple phosphorylation events (CDK5/CDK1 at Thr219/Ser251, Aurora-A at Ser251, Erk1/2) and additional modifications (palmitoylation at Cys-273 region, S-nitrosylation at Cys203) that modulate its interactions with dynein, LIS1, and other partners to control neuronal migration, nucleokinesis, centrosome maturation, ciliogenesis suppression, kinetochore function, axonal cargo selectivity at the AIS, and neurofilament assembly."},"narrative":{"mechanistic_narrative":"NDEL1 is a coiled-coil scaffold protein that functions as a central regulator of cytoplasmic dynein, controlling dynein recruitment and activation to drive neuronal migration, mitotic processes, and intracellular transport [PMID:11163260, PMID:15473966, PMID:16107726]. It directly binds LIS1, the dynein intermediate chain, and dynactin, recruiting LIS1 to dynein through the conserved intermediate-chain N-terminus; because LIS1 cannot simultaneously occupy NDEL1 and dynein, NDEL1 must hand LIS1 off in discrete steps and is itself a negative regulator that disfavors dynein-dynactin-adaptor assembly until released [PMID:14970193, PMID:18784752, PMID:37730751, PMID:37086789]. In neurons, NDEL1 acts cell-autonomously with LIS1 to couple the nucleus and centrosome during nucleokinesis, and its disruption underlies cortical migration defects, including the disease-associated p.R105P variant that ablates LIS1 binding [PMID:15473966, PMID:21092859, PMID:38194050]. NDEL1 activity is gated by a dense layer of post-translational modification: CDK5/CDK1, Aurora-A, and Erk1/2 phosphorylation, palmitoylation, and S-nitrosylation each remodel its affinity for dynein, LIS1, and partner proteins to switch transport on or off in distinct compartments [PMID:12556484, PMID:17060449, PMID:19668197, PMID:19927128, PMID:22114287, PMID:26166569, PMID:27371763]. Beyond dynein, NDEL1 organizes the centrosome and mother centriole, suppresses ciliogenesis through the trichoplein-Aurora A pathway, supports kinetochore dynein function, and bridges DISC1 into a DISC1-NDEL1-LIS1 complex relevant to neurite extension [PMID:12812986, PMID:14962739, PMID:16291865, PMID:26880200, PMID:17600710]. It additionally engages cytoskeletal and signaling systems—neurofilament and keratin intermediate filaments, the WAVE regulatory complex, Cdc42GAP, and intermediate-filament transport—and possesses an intrinsic Cys273-dependent endooligopeptidase activity required for neurite outgrowth [PMID:15208636, PMID:22453242, PMID:18331715, PMID:15728732, PMID:34319758].","teleology":[{"year":2000,"claim":"Established NDEL1 as a LIS1 partner and CDK5 substrate at centrosomes and growth cones, linking it to dynein and neuronal morphology and seeding the entire dynein-regulation model.","evidence":"Co-IP, subcellular fractionation, in vitro kinase assay and immunofluorescence in neurons","pmids":["11163260"],"confidence":"High","gaps":["Did not define how phosphorylation alters dynein binding","No structural basis for LIS1 interaction"]},{"year":2002,"claim":"Identified DISC1 as an NDEL1 binding partner whose disease-truncation abolishes binding, connecting NDEL1 to a psychiatric-disease pathway and neurite extension.","evidence":"Yeast two-hybrid, Co-IP and neurite outgrowth in PC12 cells","pmids":["12506198"],"confidence":"High","gaps":["Binding interface not mapped","Functional consequence beyond neurite length unknown"]},{"year":2003,"claim":"Mapped the DISC1-NDEL1-LIS1 trimolecular architecture and showed NDEL1 phosphorylation by CDK1/Erk1/2 and 14-3-3epsilon binding control its localization and LIS1 association, establishing NDEL1 as a phospho-regulated bridge.","evidence":"Two-hybrid and deletion mapping, in vitro kinase assays with phospho-mutants, mouse Ywhae genetics","pmids":["12812986","14962739","12556484","12796778"],"confidence":"High","gaps":["Stoichiometry of the trimolecular complex unresolved","How 14-3-3 binding mechanistically stabilizes phosphorylation unclear"]},{"year":2004,"claim":"Demonstrated NDEL1 acts upstream of dynein and in a common pathway with LIS1, directly binding dynein heavy chain to drive membrane/organelle transport and nucleus-centrosome coupling.","evidence":"In utero RNAi with LIS1 rescue epistasis, dynein/LIS1-binding mutants, lysosome motility time-lapse, neurofilament binding and polymerization assays","pmids":["15473966","14970193","15208636"],"confidence":"High","gaps":["Whether NDEL1 activates or recruits dynein not yet distinguished","Direct vs indirect effects on motor processivity untested"]},{"year":2005,"claim":"Revealed NDEL1 as a multifunctional effector—targeting dynein to microtubule plus ends via LIS1, linking CDK5 phosphorylation to katanin p60 distribution, and possessing intrinsic Cys273 endooligopeptidase activity inhibited by DISC1.","evidence":"Yeast null genetics with live imaging, Co-IP and migration assays, active-site mutagenesis with enzymatic and competitive-inhibition assays, knockout mouse","pmids":["15965467","16203747","15728732","16107726"],"confidence":"High","gaps":["Physiological substrates of the peptidase activity unidentified","Relationship between scaffolding and enzymatic functions unclear"]},{"year":2006,"claim":"Placed NDEL1 in mitotic centrosome control, showing Aurora-A phosphorylation at Ser251 and direct TACC3 interaction drive centrosome maturation and separation.","evidence":"In vitro kinase assay, phosphomimetic rescue of Aurora-A depletion, Co-IP and immunofluorescence","pmids":["17060449"],"confidence":"High","gaps":["How Ser251 phosphorylation alters dynein/LIS1 binding not defined","TACC3 recruitment mechanism incomplete"]},{"year":2007,"claim":"Defined NDEL1 kinetochore function—recruited via CENP-F to stabilize dynein/dynactin and ensure chromosome alignment—and solved the coiled-coil homodimer structure rationalizing cooperative LIS1 binding.","evidence":"Co-IP, siRNA with live imaging of chromosome behavior, X-ray crystallography of residues 10-166","pmids":["17600710","17494871","17997972"],"confidence":"High","gaps":["C-terminal cargo/dynein region not crystallized","Distinct roles of NDEL1 vs NDE1 at kinetochores not fully separated"]},{"year":2008,"claim":"Resolved how NDEL1 phosphorylation is reversed and broadened its reach, showing PP4c dephosphorylates CDK1 sites to limit katanin recruitment, NDEL1 functions in prophase nuclear-envelope invagination, and it controls Cdc42 signaling, PDE4/cAMP scaffolding, and vimentin transport.","evidence":"In vitro phosphatase assay with genetic/pharmacological epistasis, siRNA with live imaging, competitive Cdc42GAP binding and migration assays, BRET and TAP-MS","pmids":["18347064","18809722","18331715","18845247","18303022","18784752"],"confidence":"High","gaps":["Integration of these parallel functions in a single cell unclear","How LIS1 blocking of dynein is relieved mechanistically not fully defined"]},{"year":2009,"claim":"Established palmitoylation at the Cys273 region as a switch reducing dynein binding, defined NDEL1's role in retrograde axonal transport and adhesion dynamics, and placed it in an aPKC-Aurora-A-TPX2 cascade driving neurite microtubule emanation.","evidence":"Metabolic palmitoylation labeling with transport assays, antibody-blocking in DRG axons, paxillin/FAK Co-IP and adhesion assays, in vitro kinase and live MT imaging","pmids":["19927128","19522757","19492042","19668197","17202468"],"confidence":"High","gaps":["Palmitoylating enzyme(s) not identified","Crosstalk between palmitoylation and phosphorylation untested"]},{"year":2010,"claim":"Positioned NDE1/NDEL1 upstream of LIS1 for membrane dynein recruitment, identified an N-terminal dynein-IC binding domain and lamin-B-dependent spindle matrix role, and rescued PDE-driven defects, consolidating NDEL1 as the membrane dynein adaptor.","evidence":"Double siRNA epistasis with membrane fractionation, Xenopus extract spindle reconstitution with mutagenesis, neurite-outgrowth rescue with catalytic mutant","pmids":["20048338","19198602","21056974","20462516"],"confidence":"High","gaps":["How NDEL1/NDE1 associate with membranes molecularly unclear","Endopeptidase substrate during neurite outgrowth unknown"]},{"year":2011,"claim":"Defined the phosphorylation-gated motility switch: CDK5-phosphorylated NDEL1 forms a high-affinity LIS1/NDEL1/dynein complex that blocks ATP-dependent dynein release, and uncovered Dynamin 2 GTPase regulation, centrosomal microtubule anchoring, and additional partner contexts.","evidence":"Phospho-mutants and RNAi with axonal transport assays, in vitro GTPase assay, mutant mapping of centrosome targeting","pmids":["22114287","26166569","21283621","16291865"],"confidence":"High","gaps":["Reconciliation of inhibitory vs activating roles across cell types incomplete","Quantitative kinetics of LIS1 handoff not yet measured"]},{"year":2012,"claim":"Determined NDEL1's higher-order architecture (dimers/tetramers/folded-back polymers) and expanded its functions to protein quality control (misfolded Gβ to aggresome) and WAVE regulatory complex assembly for actin polymerization.","evidence":"Negative-stain EM and crosslinking-MS, Co-IP and aggresome/half-life assays, in vitro actin polymerization and cell-spreading assays","pmids":["22843697","22430153","22453242"],"confidence":"High","gaps":["Functional significance of polymeric self-assembly in cells unclear","How NDEL1 selects misfolded clients undefined"]},{"year":2013,"claim":"Placed NDEL1-dynein downstream of LIS1 for mitotic spindle orientation and showed cooperation with NudCL in retrograde mitochondrial transport.","evidence":"Lis1-mutant MEFs with rescue and live imaging, double siRNA with mitochondrial transport imaging and Co-IP","pmids":["24030547","23551859"],"confidence":"Medium","gaps":["Direct vs indirect role of NDEL1 in spindle orientation not isolated","Mechanism of NudCL cooperation unclear"]},{"year":2016,"claim":"Identified NDEL1's localization-based control of cargo polarity at the AIS via Ankyrin-G and its suppression of ciliogenesis through trichoplein-Aurora A, plus actin-bundling cooperation with Tara.","evidence":"Co-IP and live cargo tracking with fractionation, siRNA and hypomorphic mouse with co-localization, migration and synergy assays","pmids":["26844830","26880200","27546710"],"confidence":"High","gaps":["How AnkG recruitment couples to local dynein activation incompletely defined","Trigger for serum-starvation-induced NDEL1 degradation unknown"]},{"year":2017,"claim":"Provided structural and functional resolution of the DISC1-NDEL1 interface, linking it specifically to NDEL1 kinetochore attachment and mitotic timing in human cells, organoids, and patient iPSCs, and showed nNOS S-nitrosylation of Cys203 promotes dendritic arborization.","evidence":"X-ray crystallography with multi-system functional validation, biotin-switch S-nitrosylation assay with Cys203 mutant and Nos1 deletion","pmids":["29103808","27371763"],"confidence":"High","gaps":["Whether S-nitrosylation intersects with dynein regulation untested","Interplay of DISC1-controlled kinetochore role with neuronal functions unclear"]},{"year":2019,"claim":"Solved the AnkB-NDEL1 5-helix bundle structure (2:1 stoichiometry) and demonstrated that disrupting the AnkG/NDEL1 complex disrupts AIS cargo sorting, cementing the structural basis of NDEL1 AIS recruitment.","evidence":"X-ray crystallography, Co-IP, live cargo tracking and peptide competition","pmids":["31889000"],"confidence":"High","gaps":["In vivo requirement of this interface not tested","Link between ankyrin binding and dynein activation incomplete"]},{"year":2021,"claim":"Extended NDEL1's intermediate-filament role to keratins and desmosomes in epidermis, showing direct binding via a conserved IF motif and LIS1-dependent desmosomal localization.","evidence":"Direct binding assay, conditional knockout mouse with desmosome morphology analysis","pmids":["34319758"],"confidence":"Medium","gaps":["Single-lab finding without independent replication","Whether keratin/neurofilament binding share a common mechanism untested"]},{"year":2023,"claim":"Reconstituted the mechanism with purified components: NDEL1 binds the conserved dynein IC N-terminus to recruit LIS1, but because LIS1 cannot bind NDEL1 and dynein simultaneously it must be handed off in discrete steps, and NDEL1 inhibits dynein-dynactin-adaptor assembly—an effect strengthened by phosphomimetic C-terminal mutations.","evidence":"Purified-protein binding, single-molecule imaging, in vitro dynein-dynactin-adaptor reconstitution and mutagenesis across two studies","pmids":["37730751","37086789"],"confidence":"High","gaps":["Trigger that releases NDEL1 to permit handoff in cells unknown","How phosphorylation timing is coordinated with cargo loading unresolved"]},{"year":2024,"claim":"Provided direct disease causality, showing the p.R105P variant disrupts the NDEL1-LIS1 interface, impairs migration and nucleokinesis, validating the LIS1-binding interface as critical for cortical development.","evidence":"In utero electroporation, scRNA-seq and spatial transcriptomics, biochemical binding disruption, patient variant analysis","pmids":["38194050"],"confidence":"High","gaps":["Full clinical spectrum of NDEL1 variants not defined","Whether other NDEL1 interfaces contribute to disease untested"]},{"year":null,"claim":"How the dense array of NDEL1 modifications and binding partners is coordinated spatiotemporally to switch between dynein inhibition and activation in a given cell remains the central open question.","evidence":"","pmids":[],"confidence":"High","gaps":["No unified model integrating phosphorylation, palmitoylation, and S-nitrosylation timing","In-cell trigger for LIS1 handoff from NDEL1 to dynein unidentified","Physiological substrates of the endooligopeptidase activity unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[13,14,48,21]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3,4,14,49,26]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[17,49,20,47]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[30,31]},{"term_id":"GO:0016787","term_label":"hydrolase activity","supporting_discovery_ids":[30,31]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,16,40]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,14,26]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[10,11,42]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[20,24,39,43]}],"pathway":[{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[14,26,39,49]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[4,6,28,50]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[5,8,10,37]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[14,23,25,26]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[16,40]}],"complexes":["LIS1-NDEL1-dynein complex","DISC1-NDEL1-LIS1 complex","WAVE regulatory complex (WRC)","dynein-dynactin-adaptor complex"],"partners":["LIS1","DISC1","DYNEIN INTERMEDIATE CHAIN","TACC3","CENP-F","KATANIN P60","ANKYRIN-G","14-3-3EPSILON"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9GZM8","full_name":"Nuclear distribution protein nudE-like 1","aliases":["Mitosin-associated protein 1"],"length_aa":345,"mass_kda":38.4,"function":"Required for organization of the cellular microtubule array and microtubule anchoring at the centrosome. May regulate microtubule organization at least in part by targeting the microtubule severing protein KATNA1 to the centrosome. Also positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus ends. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the centripetal motion of secretory vesicles and the coupling of the nucleus and centrosome. Also required during brain development for the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Plays a role, together with DISC1, in the regulation of neurite outgrowth. Required for mitosis in some cell types but appears to be dispensible for mitosis in cortical neuronal progenitors, which instead requires NDE1. Facilitates the polymerization of neurofilaments from the individual subunits NEFH and NEFL. Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (By similarity). Plays a role, together with DISC1, in the regulation of neurite outgrowth (By similarity). May act as a RAB9A/B effector that tethers RAB9-associated late endosomes to the dynein motor for their retrograde transport to the trans-Golgi network (PubMed:34793709)","subcellular_location":"Cytoplasm, cytoskeleton; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Chromosome, centromere, kinetochore; Cytoplasm, cytoskeleton, spindle","url":"https://www.uniprot.org/uniprotkb/Q9GZM8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/NDEL1","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"DYNLL1","stoichiometry":0.2},{"gene":"DYNLL2","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NDEL1","total_profiled":1310},"omim":[{"mim_id":"618934","title":"COILED-COIL SERINE-RICH PROTEIN 1; CCSER1","url":"https://www.omim.org/entry/618934"},{"mim_id":"609449","title":"NUDE NEURODEVELOPMENT PROTEIN 1; NDE1","url":"https://www.omim.org/entry/609449"},{"mim_id":"607538","title":"NUDE NEURODEVELOPMENT PROTEIN 1-LIKE 1; NDEL1","url":"https://www.omim.org/entry/607538"},{"mim_id":"606696","title":"KATANIN, p60 SUBUNIT, A1; KATNA1","url":"https://www.omim.org/entry/606696"},{"mim_id":"605210","title":"DISC1 SCAFFOLD PROTEIN; DISC1","url":"https://www.omim.org/entry/605210"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NDEL1"},"hgnc":{"alias_symbol":["NUDEL","MITAP1","NDE1L1","NDE2"],"prev_symbol":[]},"alphafold":{"accession":"Q9GZM8","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9GZM8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9GZM8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9GZM8-F1-predicted_aligned_error_v6.png","plddt_mean":77.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NDEL1","jax_strain_url":"https://www.jax.org/strain/search?query=NDEL1"},"sequence":{"accession":"Q9GZM8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9GZM8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9GZM8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9GZM8"}},"corpus_meta":[{"pmid":"11163260","id":"PMC_11163260","title":"NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein.","date":"2000","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/11163260","citation_count":412,"is_preprint":false},{"pmid":"12796778","id":"PMC_12796778","title":"14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome.","date":"2003","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/12796778","citation_count":327,"is_preprint":false},{"pmid":"12506198","id":"PMC_12506198","title":"Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth.","date":"2002","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/12506198","citation_count":326,"is_preprint":false},{"pmid":"12812986","id":"PMC_12812986","title":"DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation.","date":"2003","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/12812986","citation_count":314,"is_preprint":false},{"pmid":"15473966","id":"PMC_15473966","title":"Ndel1 operates in a common pathway with LIS1 and cytoplasmic dynein to regulate cortical neuronal positioning.","date":"2004","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/15473966","citation_count":307,"is_preprint":false},{"pmid":"9733747","id":"PMC_9733747","title":"The Saccharomyces cerevisiae NDE1 and NDE2 genes encode separate mitochondrial NADH dehydrogenases catalyzing the oxidation of cytosolic NADH.","date":"1998","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9733747","citation_count":240,"is_preprint":false},{"pmid":"21092859","id":"PMC_21092859","title":"Genetic mosaic dissection of Lis1 and Ndel1 in neuronal migration.","date":"2010","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/21092859","citation_count":201,"is_preprint":false},{"pmid":"17202468","id":"PMC_17202468","title":"DISC1 regulates the transport of the NUDEL/LIS1/14-3-3epsilon complex through kinesin-1.","date":"2007","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/17202468","citation_count":197,"is_preprint":false},{"pmid":"14962739","id":"PMC_14962739","title":"Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders.","date":"2004","source":"Molecular and cellular neurosciences","url":"https://pubmed.ncbi.nlm.nih.gov/14962739","citation_count":187,"is_preprint":false},{"pmid":"18784752","id":"PMC_18784752","title":"LIS1 and NDEL1 coordinate the plus-end-directed transport of cytoplasmic dynein.","date":"2008","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/18784752","citation_count":154,"is_preprint":false},{"pmid":"17035248","id":"PMC_17035248","title":"DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1.","date":"2006","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/17035248","citation_count":146,"is_preprint":false},{"pmid":"17600710","id":"PMC_17600710","title":"Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtubule motor complexes.","date":"2007","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/17600710","citation_count":139,"is_preprint":false},{"pmid":"16107726","id":"PMC_16107726","title":"Complete loss of Ndel1 results in neuronal migration defects and early embryonic lethality.","date":"2005","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/16107726","citation_count":133,"is_preprint":false},{"pmid":"17060449","id":"PMC_17060449","title":"NDEL1 phosphorylation by Aurora-A kinase is essential for centrosomal maturation, separation, and TACC3 recruitment.","date":"2006","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/17060449","citation_count":124,"is_preprint":false},{"pmid":"12556484","id":"PMC_12556484","title":"Human Nudel and NudE as regulators of cytoplasmic dynein in poleward protein transport along the mitotic spindle.","date":"2003","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12556484","citation_count":119,"is_preprint":false},{"pmid":"17682047","id":"PMC_17682047","title":"NudE and NudEL are required for mitotic progression and are involved in dynein recruitment to kinetochores.","date":"2007","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/17682047","citation_count":118,"is_preprint":false},{"pmid":"14970193","id":"PMC_14970193","title":"Nudel functions in membrane traffic mainly through association with Lis1 and cytoplasmic dynein.","date":"2004","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/14970193","citation_count":108,"is_preprint":false},{"pmid":"26844830","id":"PMC_26844830","title":"Dynein Regulator NDEL1 Controls Polarized Cargo Transport at the Axon Initial Segment.","date":"2016","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/26844830","citation_count":108,"is_preprint":false},{"pmid":"19668197","id":"PMC_19668197","title":"An essential role of the aPKC-Aurora A-NDEL1 pathway in neurite elongation by modulation of microtubule dynamics.","date":"2009","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/19668197","citation_count":105,"is_preprint":false},{"pmid":"20048338","id":"PMC_20048338","title":"Functional interplay between LIS1, NDE1 and NDEL1 in dynein-dependent organelle positioning.","date":"2010","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/20048338","citation_count":102,"is_preprint":false},{"pmid":"29103808","id":"PMC_29103808","title":"DISC1 Regulates Neurogenesis via Modulating Kinetochore Attachment of Ndel1/Nde1 during Mitosis.","date":"2017","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/29103808","citation_count":102,"is_preprint":false},{"pmid":"19198602","id":"PMC_19198602","title":"Requirement for Nudel and dynein for assembly of the lamin B spindle matrix.","date":"2009","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/19198602","citation_count":97,"is_preprint":false},{"pmid":"18469341","id":"PMC_18469341","title":"Elucidating the relationship between DISC1, NDEL1 and NDE1 and the risk for schizophrenia: evidence of epistasis and competitive binding.","date":"2008","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/18469341","citation_count":93,"is_preprint":false},{"pmid":"22114287","id":"PMC_22114287","title":"A Cdk5-dependent switch regulates Lis1/Ndel1/dynein-driven organelle transport in adult axons.","date":"2011","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/22114287","citation_count":92,"is_preprint":false},{"pmid":"20007476","id":"PMC_20007476","title":"Distinct dose-dependent cortical neuronal migration and neurite extension defects in Lis1 and Ndel1 mutant mice.","date":"2009","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/20007476","citation_count":88,"is_preprint":false},{"pmid":"7671306","id":"PMC_7671306","title":"An unusual mosaic protein with a protease domain, encoded by the nudel gene, is involved in defining embryonic dorsoventral polarity in Drosophila.","date":"1995","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/7671306","citation_count":88,"is_preprint":false},{"pmid":"15965467","id":"PMC_15965467","title":"NudEL targets dynein to microtubule ends through LIS1.","date":"2005","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/15965467","citation_count":87,"is_preprint":false},{"pmid":"16203747","id":"PMC_16203747","title":"Recruitment of katanin p60 by phosphorylated NDEL1, an LIS1 interacting protein, is essential for mitotic cell division and neuronal migration.","date":"2005","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/16203747","citation_count":85,"is_preprint":false},{"pmid":"20084519","id":"PMC_20084519","title":"Evidence of statistical epistasis between DISC1, CIT and NDEL1 impacting risk for schizophrenia: biological validation with functional neuroimaging.","date":"2010","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/20084519","citation_count":81,"is_preprint":false},{"pmid":"15208636","id":"PMC_15208636","title":"A NUDEL-dependent mechanism of neurofilament assembly regulates the integrity of CNS neurons.","date":"2004","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/15208636","citation_count":79,"is_preprint":false},{"pmid":"16291865","id":"PMC_16291865","title":"Nudel contributes to microtubule anchoring at the mother centriole and is involved in both dynein-dependent and -independent centrosomal protein assembly.","date":"2005","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/16291865","citation_count":77,"is_preprint":false},{"pmid":"24030547","id":"PMC_24030547","title":"LIS1 controls mitosis and mitotic spindle organization via the LIS1-NDEL1-dynein complex.","date":"2013","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24030547","citation_count":76,"is_preprint":false},{"pmid":"17494871","id":"PMC_17494871","title":"Nudel modulates kinetochore association and function of cytoplasmic dynein in M phase.","date":"2007","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/17494871","citation_count":74,"is_preprint":false},{"pmid":"18809722","id":"PMC_18809722","title":"Lis1 and Ndel1 influence the timing of nuclear envelope breakdown in neural stem cells.","date":"2008","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/18809722","citation_count":73,"is_preprint":false},{"pmid":"21677187","id":"PMC_21677187","title":"PKA phosphorylation of NDE1 is DISC1/PDE4 dependent and modulates its interaction with LIS1 and NDEL1.","date":"2011","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/21677187","citation_count":72,"is_preprint":false},{"pmid":"17997972","id":"PMC_17997972","title":"The structure of the coiled-coil domain of Ndel1 and the basis of its interaction with Lis1, the causal protein of Miller-Dieker lissencephaly.","date":"2007","source":"Structure (London, England : 1993)","url":"https://pubmed.ncbi.nlm.nih.gov/17997972","citation_count":72,"is_preprint":false},{"pmid":"18347064","id":"PMC_18347064","title":"Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation.","date":"2008","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/18347064","citation_count":69,"is_preprint":false},{"pmid":"15728732","id":"PMC_15728732","title":"Inhibition of NUDEL (nuclear distribution element-like)-oligopeptidase activity by disrupted-in-schizophrenia 1.","date":"2005","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/15728732","citation_count":66,"is_preprint":false},{"pmid":"18331715","id":"PMC_18331715","title":"Nudel binds Cdc42GAP to modulate Cdc42 activity at the leading edge of migrating cells.","date":"2008","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/18331715","citation_count":64,"is_preprint":false},{"pmid":"26880200","id":"PMC_26880200","title":"Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein-Aurora A pathway.","date":"2016","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/26880200","citation_count":62,"is_preprint":false},{"pmid":"10625559","id":"PMC_10625559","title":"The nudel protease of Drosophila is required for eggshell biogenesis in addition to embryonic patterning.","date":"2000","source":"Developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/10625559","citation_count":55,"is_preprint":false},{"pmid":"26166569","id":"PMC_26166569","title":"Stress-Induced CDK5 Activation Disrupts Axonal Transport via Lis1/Ndel1/Dynein.","date":"2015","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/26166569","citation_count":54,"is_preprint":false},{"pmid":"27742926","id":"PMC_27742926","title":"NDE1 and NDEL1 from genes to (mal)functions: parallel but distinct roles impacting on neurodevelopmental disorders and psychiatric illness.","date":"2016","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/27742926","citation_count":52,"is_preprint":false},{"pmid":"15797709","id":"PMC_15797709","title":"Subcellular targeting of DISC1 is dependent on a domain independent from the Nudel binding site.","date":"2005","source":"Molecular and cellular neurosciences","url":"https://pubmed.ncbi.nlm.nih.gov/15797709","citation_count":52,"is_preprint":false},{"pmid":"21056974","id":"PMC_21056974","title":"Identification of a novel dynein binding domain in nudel essential for spindle pole organization in Xenopus egg extract.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21056974","citation_count":51,"is_preprint":false},{"pmid":"26010407","id":"PMC_26010407","title":"GSK-3β Phosphorylation of Cytoplasmic Dynein Reduces Ndel1 Binding to Intermediate Chains and Alters Dynein Motility.","date":"2015","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/26010407","citation_count":47,"is_preprint":false},{"pmid":"9735365","id":"PMC_9735365","title":"Role of Nudel protease activation in triggering dorsoventral polarization of the Drosophila embryo.","date":"1998","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/9735365","citation_count":43,"is_preprint":false},{"pmid":"18303022","id":"PMC_18303022","title":"Ndel1 controls the dynein-mediated transport of vimentin during neurite outgrowth.","date":"2008","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/18303022","citation_count":42,"is_preprint":false},{"pmid":"19492042","id":"PMC_19492042","title":"Nudel and FAK as antagonizing strength modulators of nascent adhesions through paxillin.","date":"2009","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/19492042","citation_count":41,"is_preprint":false},{"pmid":"19927128","id":"PMC_19927128","title":"Ndel1 palmitoylation: a new mean to regulate cytoplasmic dynein activity.","date":"2009","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/19927128","citation_count":41,"is_preprint":false},{"pmid":"17221205","id":"PMC_17221205","title":"Expression patterns of LIS1, dynein and their interaction partners dynactin, NudE, NudEL and NudC in human gliomas suggest roles in invasion and proliferation.","date":"2007","source":"Acta neuropathologica","url":"https://pubmed.ncbi.nlm.nih.gov/17221205","citation_count":41,"is_preprint":false},{"pmid":"11231056","id":"PMC_11231056","title":"NudE-L, a novel Lis1-interacting protein, belongs to a family of vertebrate coiled-coil proteins.","date":"2001","source":"Mechanisms of development","url":"https://pubmed.ncbi.nlm.nih.gov/11231056","citation_count":41,"is_preprint":false},{"pmid":"24093049","id":"PMC_24093049","title":"NDE1 and NDEL1: twin neurodevelopmental proteins with similar 'nature' but different 'nurture'.","date":"2013","source":"Biomolecular concepts","url":"https://pubmed.ncbi.nlm.nih.gov/24093049","citation_count":38,"is_preprint":false},{"pmid":"23551859","id":"PMC_23551859","title":"Distinct functions of nuclear distribution proteins LIS1, Ndel1 and NudCL in regulating axonal mitochondrial transport.","date":"2013","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/23551859","citation_count":38,"is_preprint":false},{"pmid":"30940662","id":"PMC_30940662","title":"NFAT1-Mediated Regulation of NDEL1 Promotes Growth and Invasion of Glioma Stem-like Cells.","date":"2019","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/30940662","citation_count":36,"is_preprint":false},{"pmid":"22843697","id":"PMC_22843697","title":"The mitosis and neurodevelopment proteins NDE1 and NDEL1 form dimers, tetramers, and polymers with a folded back structure in solution.","date":"2012","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22843697","citation_count":36,"is_preprint":false},{"pmid":"18845247","id":"PMC_18845247","title":"Ndel1 alters its conformation by sequestering cAMP-specific phosphodiesterase-4D3 (PDE4D3) in a manner that is dynamically regulated through Protein Kinase A (PKA).","date":"2008","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/18845247","citation_count":34,"is_preprint":false},{"pmid":"20462516","id":"PMC_20462516","title":"Assessing the role of endooligopeptidase activity of Ndel1 (nuclear-distribution gene E homolog like-1) in neurite outgrowth.","date":"2010","source":"Molecular and cellular neurosciences","url":"https://pubmed.ncbi.nlm.nih.gov/20462516","citation_count":34,"is_preprint":false},{"pmid":"8844153","id":"PMC_8844153","title":"The maternal nudel protein of Drosophila has two distinct roles important for embryogenesis.","date":"1996","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/8844153","citation_count":33,"is_preprint":false},{"pmid":"20168084","id":"PMC_20168084","title":"The essential role of LIS1, NDEL1 and Aurora-A in polarity formation and microtubule organization during neurogensis.","date":"2010","source":"Cell adhesion & migration","url":"https://pubmed.ncbi.nlm.nih.gov/20168084","citation_count":33,"is_preprint":false},{"pmid":"23388542","id":"PMC_23388542","title":"Plasma Ndel1 enzyme activity is reduced in patients with schizophrenia--a potential biomarker?","date":"2013","source":"Journal of psychiatric research","url":"https://pubmed.ncbi.nlm.nih.gov/23388542","citation_count":32,"is_preprint":false},{"pmid":"19522757","id":"PMC_19522757","title":"Nudel promotes axonal lysosome clearance and endo-lysosome formation via dynein-mediated transport.","date":"2009","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/19522757","citation_count":32,"is_preprint":false},{"pmid":"21948775","id":"PMC_21948775","title":"Ndel1, Nudel (Noodle): flexible in the cell?","date":"2011","source":"Cytoskeleton (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/21948775","citation_count":30,"is_preprint":false},{"pmid":"34269216","id":"PMC_34269216","title":"miR-103-3p targets Ndel1 to regulate neural stem cell proliferation and differentiation.","date":"2022","source":"Neural regeneration research","url":"https://pubmed.ncbi.nlm.nih.gov/34269216","citation_count":25,"is_preprint":false},{"pmid":"37730751","id":"PMC_37730751","title":"Conserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dynein.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/37730751","citation_count":23,"is_preprint":false},{"pmid":"26476704","id":"PMC_26476704","title":"Increased expression of NDEL1 and MBP genes in the peripheral blood of antipsychotic-naïve patients with first-episode psychosis.","date":"2015","source":"European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/26476704","citation_count":22,"is_preprint":false},{"pmid":"19622634","id":"PMC_19622634","title":"Opposing effects of Ndel1 and alpha1 or alpha2 on cytoplasmic dynein through competitive binding to Lis1.","date":"2009","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/19622634","citation_count":22,"is_preprint":false},{"pmid":"27546710","id":"PMC_27546710","title":"Regulation of the actin cytoskeleton by the Ndel1-Tara complex is critical for cell migration.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27546710","citation_count":21,"is_preprint":false},{"pmid":"25698733","id":"PMC_25698733","title":"DBZ regulates cortical cell positioning and neurite development by sustaining the anterograde transport of Lis1 and DISC1 through control of Ndel1 dual-phosphorylation.","date":"2015","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/25698733","citation_count":20,"is_preprint":false},{"pmid":"35493069","id":"PMC_35493069","title":"Nde1 and Ndel1: Outstanding Mysteries in Dynein-Mediated Transport.","date":"2022","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/35493069","citation_count":19,"is_preprint":false},{"pmid":"37086789","id":"PMC_37086789","title":"Ndel1 disfavors dynein-dynactin-adaptor complex formation in two distinct ways.","date":"2023","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/37086789","citation_count":19,"is_preprint":false},{"pmid":"15147871","id":"PMC_15147871","title":"Expression of NUDEL in manchette and its implication in spermatogenesis.","date":"2004","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/15147871","citation_count":18,"is_preprint":false},{"pmid":"24785679","id":"PMC_24785679","title":"The expression and roles of Nde1 and Ndel1 in the adult mammalian central nervous system.","date":"2014","source":"Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/24785679","citation_count":18,"is_preprint":false},{"pmid":"10628985","id":"PMC_10628985","title":"Biochemical defects of mutant nudel alleles causing early developmental arrest or dorsalization of the Drosophila embryo.","date":"2000","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/10628985","citation_count":18,"is_preprint":false},{"pmid":"27307241","id":"PMC_27307241","title":"Ndel1 and Reelin Maintain Postnatal CA1 Hippocampus Integrity.","date":"2016","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/27307241","citation_count":17,"is_preprint":false},{"pmid":"31889000","id":"PMC_31889000","title":"Mechanistic insights into the interactions of dynein regulator Ndel1 with neuronal ankyrins and implications in polarity maintenance.","date":"2019","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/31889000","citation_count":17,"is_preprint":false},{"pmid":"32717241","id":"PMC_32717241","title":"Arsenic trioxide disturbs the LIS1/NDEL1/dynein microtubule dynamic complex by disrupting the CLIP170 zinc finger in head and neck cancer.","date":"2020","source":"Toxicology and applied pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/32717241","citation_count":17,"is_preprint":false},{"pmid":"22453242","id":"PMC_22453242","title":"Nudel is crucial for the WAVE complex assembly in vivo by selectively promoting subcomplex stability and formation through direct interactions.","date":"2012","source":"Cell research","url":"https://pubmed.ncbi.nlm.nih.gov/22453242","citation_count":16,"is_preprint":false},{"pmid":"30857875","id":"PMC_30857875","title":"Ndel1 oligopeptidase activity as a potential biomarker of early stages of schizophrenia.","date":"2019","source":"Schizophrenia research","url":"https://pubmed.ncbi.nlm.nih.gov/30857875","citation_count":15,"is_preprint":false},{"pmid":"30321766","id":"PMC_30321766","title":"Oligopeptidases activity in bipolar disorder: Ndel1 and angiotensin I converting enzyme.","date":"2018","source":"Journal of affective disorders","url":"https://pubmed.ncbi.nlm.nih.gov/30321766","citation_count":14,"is_preprint":false},{"pmid":"24680936","id":"PMC_24680936","title":"NDEL1 was decreased in the CA3 region but increased in the hippocampal blood vessel network during the spontaneous seizure period after pilocarpine-induced status epilepticus.","date":"2014","source":"Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/24680936","citation_count":14,"is_preprint":false},{"pmid":"22430153","id":"PMC_22430153","title":"Misfolded Gβ is recruited to cytoplasmic dynein by Nudel for efficient clearance.","date":"2012","source":"Cell research","url":"https://pubmed.ncbi.nlm.nih.gov/22430153","citation_count":13,"is_preprint":false},{"pmid":"26851141","id":"PMC_26851141","title":"Genome-wide investigation of schizophrenia associated plasma Ndel1 enzyme activity.","date":"2016","source":"Schizophrenia research","url":"https://pubmed.ncbi.nlm.nih.gov/26851141","citation_count":12,"is_preprint":false},{"pmid":"23213412","id":"PMC_23213412","title":"Ndel1-derived peptides modulate bidirectional transport of injected beads in the squid giant axon.","date":"2012","source":"Biology open","url":"https://pubmed.ncbi.nlm.nih.gov/23213412","citation_count":12,"is_preprint":false},{"pmid":"25961396","id":"PMC_25961396","title":"Protein-Protein and Peptide-Protein Interactions of NudE-Like 1 (Ndel1): A Protein Involved in Schizophrenia.","date":"2015","source":"Current protein & peptide science","url":"https://pubmed.ncbi.nlm.nih.gov/25961396","citation_count":11,"is_preprint":false},{"pmid":"33615226","id":"PMC_33615226","title":"Behavioral Deficits in Mice with Postnatal Disruption of Ndel1 in Forebrain Excitatory Neurons: Implications for Epilepsy and Neuropsychiatric Disorders.","date":"2021","source":"Cerebral cortex communications","url":"https://pubmed.ncbi.nlm.nih.gov/33615226","citation_count":11,"is_preprint":false},{"pmid":"32423231","id":"PMC_32423231","title":"Role of NDEL1 and VEGF/VEGFR-2 in Mouse Hippocampus After Status Epilepticus.","date":"2020","source":"ASN neuro","url":"https://pubmed.ncbi.nlm.nih.gov/32423231","citation_count":10,"is_preprint":false},{"pmid":"16005531","id":"PMC_16005531","title":"Cloning and characterization of the human and rabbit NUDEL-oligopeptidase promoters and their negative regulation.","date":"2005","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/16005531","citation_count":10,"is_preprint":false},{"pmid":"33422130","id":"PMC_33422130","title":"Expression and function of Ndel1 during the differentiation of neural stem cells induced by hippocampal exosomesticle.","date":"2021","source":"Stem cell research & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/33422130","citation_count":10,"is_preprint":false},{"pmid":"11984873","id":"PMC_11984873","title":"Evidence for a glycosaminoglycan on the nudel protein important for dorsoventral patterning of the drosophila embryo.","date":"2002","source":"Developmental dynamics : an official publication of the American Association of Anatomists","url":"https://pubmed.ncbi.nlm.nih.gov/11984873","citation_count":10,"is_preprint":false},{"pmid":"38194050","id":"PMC_38194050","title":"Novel lissencephaly-associated NDEL1 variant reveals distinct roles of NDE1 and NDEL1 in nucleokinesis and human cortical malformations.","date":"2024","source":"Acta neuropathologica","url":"https://pubmed.ncbi.nlm.nih.gov/38194050","citation_count":9,"is_preprint":false},{"pmid":"27298008","id":"PMC_27298008","title":"Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain.","date":"2016","source":"Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/27298008","citation_count":9,"is_preprint":false},{"pmid":"27371763","id":"PMC_27371763","title":"Developmental Alcohol Exposure Impairs Activity-Dependent S-Nitrosylation of NDEL1 for Neuronal Maturation.","date":"2017","source":"Cerebral cortex (New York, N.Y. : 1991)","url":"https://pubmed.ncbi.nlm.nih.gov/27371763","citation_count":9,"is_preprint":false},{"pmid":"30539652","id":"PMC_30539652","title":"Nudel involvement in the high-glucose-induced epithelial-mesenchymal transition of tubular epithelial cells.","date":"2018","source":"American journal of physiology. Renal physiology","url":"https://pubmed.ncbi.nlm.nih.gov/30539652","citation_count":8,"is_preprint":false},{"pmid":"33116174","id":"PMC_33116174","title":"Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33116174","citation_count":8,"is_preprint":false},{"pmid":"32328622","id":"PMC_32328622","title":"Reelin Improves Cognition and Extends the Lifespan of Mutant Ndel1 Mice with Postnatal CA1 Hippocampus Deterioration.","date":"2020","source":"Cerebral cortex (New York, N.Y. : 1991)","url":"https://pubmed.ncbi.nlm.nih.gov/32328622","citation_count":8,"is_preprint":false},{"pmid":"36711700","id":"PMC_36711700","title":"Conserved Roles for the Dynein Intermediate Chain and Ndel1 in Assembly and Activation of Dynein.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/36711700","citation_count":7,"is_preprint":false},{"pmid":"35465088","id":"PMC_35465088","title":"LIS1 and NDEL1 Regulate Axonal Trafficking of Mitochondria in Mature Neurons.","date":"2022","source":"Frontiers in molecular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/35465088","citation_count":7,"is_preprint":false},{"pmid":"34319758","id":"PMC_34319758","title":"Roles for Ndel1 in keratin organization and desmosome function.","date":"2021","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/34319758","citation_count":6,"is_preprint":false},{"pmid":"21283621","id":"PMC_21283621","title":"The cytoskeletal protein Ndel1 regulates dynamin 2 GTPase activity.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/21283621","citation_count":6,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":48946,"output_tokens":12146,"usd":0.164514,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":23324,"output_tokens":6695,"usd":0.141997,"stage2_stop_reason":"end_turn"},"total_usd":0.306511,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"NUDEL (NDEL1) was identified as a novel LIS1-interacting protein and a substrate of Cdk5 kinase. NUDEL is enriched at centrosomes and neuronal growth cones and interacts with cytoplasmic dynein. Inhibition of Cdk5 modifies NUDEL distribution in neurons and affects neuritic morphology.\",\n      \"method\": \"Co-immunoprecipitation, subcellular fractionation, in vitro kinase assay, immunofluorescence\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, direct kinase substrate assay, replicated across multiple methods in a focused study\",\n      \"pmids\": [\"11163260\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"14-3-3epsilon binds to CDK5/p35-phosphorylated NUDEL and this binding maintains NUDEL phosphorylation. Deficiency of 14-3-3epsilon results in mislocalization of NUDEL and LIS1, consistent with reduction of cytoplasmic dynein function.\",\n      \"method\": \"Co-immunoprecipitation, genetic mouse models (Ywhae knockout/heterozygous), immunolocalization\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (Co-IP, mouse genetics, immunolocalization), replicated in vivo\",\n      \"pmids\": [\"12796778\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"DISC1 interacts with NUDEL (NDEL1) via yeast two-hybrid, and the disease-associated truncation mutant of DISC1 fails to bind NUDEL. Expression of mutant DISC1 in PC12 cells reduces neurite extension.\",\n      \"method\": \"Yeast two-hybrid, co-immunoprecipitation, neurite outgrowth assay in PC12 cells\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — replicated across multiple studies with two orthogonal binding assays plus functional readout\",\n      \"pmids\": [\"12506198\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"DISC1 interacts with NUDEL through a central coiled-coil domain of DISC1 that binds the C-terminal domain of NUDEL, independent from the LIS1 binding site on NUDEL. NUDEL acts as a bridge between DISC1 and LIS1, allowing formation of a trimolecular complex.\",\n      \"method\": \"Yeast two-hybrid, mammalian two-hybrid, co-immunoprecipitation, deletion mapping\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple binding assays across independent studies with domain mapping\",\n      \"pmids\": [\"12812986\", \"14962739\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Ndel1 positively regulates dynein activity by facilitating the interaction between LIS1 and dynein. Loss of Ndel1 in developing neocortex impairs neuronal positioning and causes uncoupling of the centrosome and nucleus. Overexpression of LIS1 partially rescues the positioning defect caused by Ndel1 RNAi, placing Ndel1 upstream of dynein and in common pathway with LIS1.\",\n      \"method\": \"RNA interference in developing neocortex (in utero), epistasis rescue experiments, immunofluorescence\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis with rescue experiments, multiple orthogonal approaches, in vivo\",\n      \"pmids\": [\"15473966\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Nudel (NDEL1) is specifically phosphorylated in M phase by Cdc2 (CDK1) and by Erk1/2. Phosphorylation regulates its cell-cycle-dependent distribution and increases its association with Lis1. A Nudel mutant incapable of binding Lis1 impaired poleward movement of dynein and dynein-mediated transport of kinetochore proteins to spindle poles.\",\n      \"method\": \"In vitro kinase assays, phosphorylation-mimicking and phosphorylation-deficient mutants, immunofluorescence, functional mitosis assays\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro kinase assay, mutagenesis, functional readout in M phase, single lab\",\n      \"pmids\": [\"12556484\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Complete loss of Ndel1 results in embryonic lethality at the peri-implantation stage and cell proliferation defects. Compound heterozygous mice show neuronal migration defects. Ndel1 loss leads to abnormalities in microtubule organization and similar defects in dynein-dependent vesicle distribution as Lis1 loss. Rescue by LIS1, NDEL1, or NDE1 overexpression confirms they act in a common pathway.\",\n      \"method\": \"Targeted gene disruption (mouse knockout/hypomorph), MEF and granule cell assays, immunofluorescence, rescue experiments\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO mouse, epistasis rescue, multiple cell types and readouts\",\n      \"pmids\": [\"16107726\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"CDK5-mediated phosphorylation of NDEL1 facilitates interaction between NDEL1 and katanin p60, and phosphorylated NDEL1 regulates the distribution of katanin p60. Loss of NDEL1 causes abnormal accumulation of p60 in nucleus. Loss of NDEL1 or dominant negative p60 in migrating neurons causes defective migration and elongation of nuclear-centrosomal distance.\",\n      \"method\": \"Co-immunoprecipitation, phosphorylation assays, dominant-negative expression, neuronal migration assay\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP, in vivo migration assay, phosphorylation-function link, single lab multiple methods\",\n      \"pmids\": [\"16203747\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Aurora-A phosphorylates NDEL1 at Ser251 at mitotic entry. This phosphorylation is required for centrosomal maturation and separation. NDEL1 is required for centrosome targeting of TACC3 through direct interaction with TACC3. Aurora-A phosphorylation-mimetic NDEL1 mutants rescue centrosomal maturation/separation defects in Aurora-A-depleted cells.\",\n      \"method\": \"In vitro kinase assay, phosphomimetic/phosphodeficient mutants, siRNA depletion rescue, immunofluorescence, co-immunoprecipitation\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro kinase assay, mutagenesis rescue, co-IP for TACC3 interaction, single lab\",\n      \"pmids\": [\"17060449\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"DISC1 directly interacts with kinesin-1 heavy chain and links the NUDEL/LIS1/14-3-3epsilon complex to kinesin-1 for anterograde axonal transport. Knockdown of DISC1 inhibited accumulation of NUDEL, LIS1, and 14-3-3epsilon at axons and inhibited axon elongation.\",\n      \"method\": \"Co-immunoprecipitation, RNAi knockdown, immunofluorescence, axon elongation assay\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, RNAi with functional readout, single lab\",\n      \"pmids\": [\"17202468\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Cenp-F interacts with Ndel1 and Nde1, and Ndel1/Nde1/Lis1 localize to kinetochores in a Cenp-F-dependent manner. Inhibition of Ndel1 leads to chromosome malalignments not detected by the spindle checkpoint, resulting in lagging chromosomes during anaphase. Ndel1 and Nde1 play distinct roles at kinetochores.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, live cell imaging, immunofluorescence\",\n      \"journal\": \"Current biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, RNAi with defined cellular phenotype, functional distinction between Ndel1 and Nde1, multiple orthogonal methods\",\n      \"pmids\": [\"17600710\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Ndel1 is required for robust localization of dynein/dynactin at the kinetochore. Kinetochore localization of Nudel depends mostly (~78%) on mitosin (CENP-F) and slightly on dynein/dynactin. Nudel activates dynein-mediated protein transport at the kinetochore and stabilizes kinetochore dynein/dynactin against microtubule-dependent stripping.\",\n      \"method\": \"RNAi, mutant overexpression, time-lapse imaging, immunofluorescence\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi with defined kinetochore phenotype, mutant analysis, single lab\",\n      \"pmids\": [\"17494871\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Crystal structure of two fragments of the coiled-coil domain of Ndel1 (residues 10-166) revealed a stable parallel homodimer with supercoiled alpha helices. The structure suggests how the Lis1-interacting domain can be regulated via cooperative binding of two Ndel1 helices to a Lis1 homodimer.\",\n      \"method\": \"X-ray crystallography, solution studies (solution NMR/biophysics)\",\n      \"journal\": \"Structure\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure with complementary solution studies, single study\",\n      \"pmids\": [\"17997972\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"NUDEL directly interacts with neurofilament light subunit (NF-L) and facilitates the polymerization of neurofilaments. Knockdown of NUDEL by RNAi destabilizes NF-L and alters neurofilament homeostasis, resulting in morphological changes reminiscent of neurodegeneration.\",\n      \"method\": \"Co-immunoprecipitation, RNAi knockdown in neuroblastoma cells and primary cortical neurons, in vitro polymerization assay\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — direct interaction assay, in vitro polymerization assay, RNAi in multiple systems, single lab\",\n      \"pmids\": [\"15208636\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Nudel (NDEL1) regulates dynein-mediated membrane transport through direct interactions with both Lis1 and dynein heavy chain. A Nudel mutant defective in Lis1 or dynein heavy chain binding causes dispersion of dynein-dependent membranous organelles and reduces frequency and velocity of lysosome minus-end-directed motions.\",\n      \"method\": \"Mutant overexpression, RNAi, time-lapse microscopy for lysosome motility, organelle localization assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — structure-function mutants, time-lapse imaging with quantitative motility analysis, single lab\",\n      \"pmids\": [\"14970193\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Nudel (Ndl1 in budding yeast) targets dynein to microtubule plus ends through LIS1. The Ndl1 null mutant shows decreased targeting of dynein to microtubule plus ends. Ndl1 regulates dynein targeting through LIS1 but not through CLIP170.\",\n      \"method\": \"Yeast genetics (null mutant), live cell imaging, biochemical interaction assays\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic null in yeast ortholog, live imaging, biochemical confirmation, multiple approaches\",\n      \"pmids\": [\"15965467\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Nudel (NDEL1) contributes to microtubule anchoring at the mother centriole. Nudel localizes to mother centriole and its centrosome localization requires a C-terminal region essential for associations with dynein, dynactin, PCM-1, pericentrin, and gamma-tubulin. Nudel plays roles in both dynein-mediated transport of dynactin/Lis1/PCM-1 and dynein-independent centrosomal targeting of pericentrin and gamma-tubulin.\",\n      \"method\": \"RNAi, mutant overexpression, immunofluorescence, co-immunoprecipitation\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi with defined phenotype, mutant mapping, co-IP, single lab\",\n      \"pmids\": [\"16291865\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"LIS1 suppresses the motility of cytoplasmic dynein on microtubules, while NDEL1 releases the blocking effect of LIS1 on cytoplasmic dynein. LIS1 mediates anterograde transport of cytoplasmic dynein as a dynein-LIS1 complex on transportable microtubule fragments.\",\n      \"method\": \"In vitro microtubule motility assay, blocking antibody experiments, co-immunoprecipitation\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro motility reconstitution, antibody blocking, Co-IP, single lab\",\n      \"pmids\": [\"18784752\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Protein phosphatase 4 catalytic subunit (PP4c) dephosphorylates NDEL1 at CDK1 sites. Loss of PP4c leads to unscheduled CDK1 activation and abnormal NDEL1 phosphorylation, which causes excessive recruitment of katanin p60 to the centrosome and microtubule disorganization. Inhibition of CDK1, NDEL1, or katanin p60 rescues the defects caused by PP4 inhibition.\",\n      \"method\": \"In vitro phosphatase assay, targeted gene disruption, pharmacological CDK1 inhibition, epistasis rescue\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro phosphatase assay, genetic KO, pharmacological epistasis, multiple orthogonal methods\",\n      \"pmids\": [\"18347064\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Lis1 and Ndel1 reduction impairs prophase nuclear envelope invagination (PNEI), a dynein-dependent process facilitating nuclear envelope breakdown (NEBD). Ndel1 phosphorylation is important for this function, regulating binding to both Lis1 and dynein.\",\n      \"method\": \"siRNA knockdown, live cell imaging, phosphomimetic/phosphodeficient mutants, mouse brain histology\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA with live imaging, mutagenesis, in vivo validation, single lab\",\n      \"pmids\": [\"18809722\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Nudel interacts with Cdc42GAP and competes with Cdc42 for binding Cdc42GAP, inhibiting Cdc42GAP-mediated inactivation of Cdc42 in a dose-dependent manner. Nudel's leading-edge localization in migrating cells requires phosphorylation by Erk1/2. Depleting Nudel or expressing a non-phosphorylatable mutant abolishes Cdc42 activation and cell migration.\",\n      \"method\": \"Co-immunoprecipitation, competitive binding assay, RNAi, phosphomimetic mutants, Cdc42 activation assay, migration assay\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — competitive binding assay, RNAi with functional readout, Erk phosphorylation-localization link, multiple approaches single lab\",\n      \"pmids\": [\"18331715\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Ndel1 forms a novel complex with vimentin, dynein, Lis1, and alphaCOP. Ndel1 promotes interaction between Lis1, alphaCOP, and the vimentin-dynein complex, activating dynein-mediated transport of vimentin. Loss of Ndel1 by RNAi fails to incorporate Lis1/alphaCOP in the complex, reduces vimentin transport, and alters neuritogenesis.\",\n      \"method\": \"Tandem affinity purification, co-immunoprecipitation, RNAi, transport assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — TAP-MS identification, co-IP validation, RNAi with functional readout, single lab\",\n      \"pmids\": [\"18303022\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"aPKC phosphorylates Aurora A at Thr287, which facilitates Aurora A interaction with TPX2 and activates Aurora A at the neurite hillock, leading to phosphorylation of NDEL1 at S251 and NDEL1 recruitment. Suppression of aPKC, Aurora A, TPX2, or Ndel1 impairs neurite extension. Suppression of this pathway decreases frequency of microtubule emanation from the MTOC.\",\n      \"method\": \"In vitro kinase assays, RNAi, phosphomimetic mutants, live microtubule plus-end marker imaging, immunofluorescence\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro kinase assay, live imaging of MT dynamics, RNAi pathway placement, multiple methods single lab\",\n      \"pmids\": [\"19668197\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Palmitoylation of Ndel1 by specific palmitoylation enzymes occurs in vivo. Unpalmitoylated Ndel1 interacts better with dynein; palmitoylated Ndel1 reduces cytoplasmic dynein activity, as shown by Golgi distribution, vesicle trafficking, retrograde transport of dynein, and neuronal migration assays.\",\n      \"method\": \"Palmitoylation assay (metabolic labeling), co-immunoprecipitation, organelle localization assays, neuronal migration assay, time-lapse imaging\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct palmitoylation detection, multiple functional readouts, mechanistic link between modification and dynein binding, single lab\",\n      \"pmids\": [\"19927128\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Nudel binds to paxillin at nascent adhesions and colocalization is observed in areas of active membrane protrusions. Focal adhesion kinase (FAK) disrupts the Nudel-paxillin interaction in a paxillin-binding-dependent manner. Forced localization of Nudel to all focal contacts markedly strengthened adhesivity, while overexpression of activated FAK caused cell edge shrinkage.\",\n      \"method\": \"Co-immunoprecipitation, fusion protein forced localization, RNAi, cell migration assays, immunofluorescence\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, structure-function analysis, functional migration/adhesion assays, single lab\",\n      \"pmids\": [\"19492042\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Nudel is required for retrograde axonal transport in DRG neurons; anti-Nudel antibody injection abolishes retrograde transport of membranous organelles and leads to lysosome accumulation in axons and delayed endo-lysosome formation.\",\n      \"method\": \"Microinjection of blocking antibody into cultured DRG neurons, time-lapse microscopy, Golgi and lysosome localization assays\",\n      \"journal\": \"Traffic\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct antibody perturbation in neurons, time-lapse imaging, defined phenotypic readout, single lab\",\n      \"pmids\": [\"19522757\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Depletion of both NDE1 and NDEL1 causes striking dispersal of Golgi and endocytic organelles and complete loss of dynein from membranes. A substantial portion of NDE1 and NDEL1 is membrane-associated. NDE1 and NDEL1 act upstream of LIS1 in dynein recruitment on membrane: exogenous NDE1 or NDEL1 rescues LIS1 depletion effects on Golgi, while LIS1 only partially rescues loss of NDE1 and NDEL1.\",\n      \"method\": \"siRNA knockdown (single and double), organelle localization imaging, membrane fractionation, epistasis rescue experiments\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — double KD epistasis, fractionation, rescue experiments, single lab multiple methods\",\n      \"pmids\": [\"20048338\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Nudel/Ndel1 regulates microtubule organization during spindle assembly independently of kinetochore functions. Nudel directly interacts with lamin B to facilitate lamin-B-containing matrix accumulation and assembly on microtubules in a dynein-dependent manner. A novel dynein binding domain within the first 80 amino acids of Nudel was identified that interacts with dynein intermediate chain.\",\n      \"method\": \"Xenopus egg extract spindle assembly assay, immunodepletion, protein binding assays, extensive mutagenesis\",\n      \"journal\": \"Nature cell biology / The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — reconstitution in Xenopus extract, mutagenesis, biochemical binding assays, identifies specific domain\",\n      \"pmids\": [\"19198602\", \"21056974\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Genetic mosaic analysis (MADM) established that Ndel1 is required cell-autonomously for a specific late step of neuronal migration: entry into the target lamina, distinct from Lis1's role in migration efficiency.\",\n      \"method\": \"Mosaic Analysis with Double Markers (MADM), in vivo sparse clonal analysis in mouse cortex\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — rigorous in vivo genetic mosaic analysis, cell-autonomous function established at single-cell resolution\",\n      \"pmids\": [\"21092859\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Cdk5-phosphorylated Ndel1 promotes a high-affinity Lis1/Ndel1/dynein complex that blocks ATP-dependent release of dynein from microtubules, inhibiting processive motility. In adult axons, unphosphorylated Ndel1 inhibits dynein-mediated transport; Cdk5 phosphorylation of Ndel1 releases this inhibition and allows Lis1 to further stimulate cargo transport.\",\n      \"method\": \"RNAi, phosphorylation mutants, organelle transport assays in adult DRG axons, dominant-negative Cdk5\",\n      \"journal\": \"The Journal of neuroscience / Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple studies with phosphomimetics, RNAi, dominant negatives, consistent mechanistic conclusion\",\n      \"pmids\": [\"22114287\", \"26166569\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"NUDEL possesses endooligopeptidase (cysteine protease) activity; mutation of Cys-273 fully abolishes this activity without disrupting secondary structure. DISC1 inhibits NUDEL-oligopeptidase activity in a competitive fashion, and the catalytic site is close to the DISC1-binding site on NUDEL.\",\n      \"method\": \"Site-directed mutagenesis of catalytic Cys-273, enzymatic activity assay, competitive inhibition assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — active-site mutagenesis with enzymatic assay, competitive inhibition kinetics, single lab\",\n      \"pmids\": [\"15728732\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"The endooligopeptidase activity of Ndel1 is functionally important for neurite outgrowth in PC12 cells. Wild-type Ndel1 increases neurite-bearing cells; the catalytically dead mutant Ndel1(C273A) decreases neurite outgrowth; and RNAi depletion of Ndel1 is rescued by enzymatically active Ndel1(WT) but not Ndel1(C273A).\",\n      \"method\": \"RNAi, rescue with wild-type vs. catalytic mutant, neurite outgrowth quantification in PC12 cells\",\n      \"journal\": \"Molecular and cellular neurosciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi rescue with catalytic mutant provides mechanistic specificity, single lab\",\n      \"pmids\": [\"20462516\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Ndel1 directly interacts with PDE4 family members, and the interaction with PDE4D3 is specifically disrupted by PKA phosphorylation at Ser13 of PDE4D3. Ndel1 sequesters EPAC (but not PKA) to form a cAMP signaling complex. Ndel1 self-interaction (dimerization) is stabilized by PDE4 binding.\",\n      \"method\": \"Co-immunoprecipitation, BRET interaction assay in living cells, peptide array mapping, PKA phosphorylation assay\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — BRET in living cells, Co-IP, peptide array, single lab with multiple methods\",\n      \"pmids\": [\"18845247\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"PKA phosphorylates NDE1 at threonine-131 (T131) in a DISC1/PDE4-dependent manner. T131 phosphorylation modulates NDE1-LIS1 and NDE1-NDEL1 interactions, as confirmed by homology modeling and experimental binding assays. Mutation of T131 to mimic PKA phosphorylation inhibits neurite outgrowth.\",\n      \"method\": \"In vitro kinase assay, co-immunoprecipitation, homology modeling, neurite outgrowth assay, immunofluorescence\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — kinase assay, binding assays, functional readout, but primarily focused on NDE1; NDEL1 interaction is a secondary finding\",\n      \"pmids\": [\"21677187\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Full-length NDEL1 forms dimers, tetramers, and chain-like polymers with a folded-back structure in solution. The C-terminal region, required for interaction with dynein and DISC1, folds back onto the N-terminal coiled-coil domain. NDE1 and NDEL1 can interact directly to form mixed complexes.\",\n      \"method\": \"Negative stain electron microscopy, chemical cross-linking/mass spectrometry, isotope labeling, biophysical characterization\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — structural EM, cross-linking MS, multiple biophysical methods, single study\",\n      \"pmids\": [\"22843697\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Nudel directly interacts with misfolded Gβ (mfGβ) and recruits it to cytoplasmic dynein for transport to the centrosome/aggresome. Depletion of Nudel by RNAi reduces dynein-associated mfGβ, impairs aggresome formation, and prolongs the half-life of nascent Gβ.\",\n      \"method\": \"Co-immunoprecipitation, RNAi, half-life measurement, aggresome formation assay\",\n      \"journal\": \"Cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, RNAi with defined functional readout (protein quality control), single lab\",\n      \"pmids\": [\"22430153\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Nudel is crucial for in vivo assembly of the WAVE regulatory complex (WRC). Nudel stabilizes the Sra1-Nap1-Abi1 subcomplex through dynamic binding to Sra1 and protects HSPC300 from proteasomal degradation, stimulating HSPC300-WAVE2 complex formation. Depletion of Nudel abolishes WRC-dependent actin polymerization in vitro and Rac1-induced lamellipodial actin networks.\",\n      \"method\": \"Co-immunoprecipitation, RNAi, in vitro actin polymerization assay, cell spreading assay\",\n      \"journal\": \"Cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro actin assay, RNAi, Co-IP for subcomplex interactions, single lab\",\n      \"pmids\": [\"22453242\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"LIS1 is required for mitotic spindle organization via the LIS1-NDEL1-dynein complex. Overexpression of NDEL1-dynein and microtubule stabilization rescues spindle orientation defects in Lis1 mutants, placing NDEL1-dynein downstream of LIS1 in spindle orientation.\",\n      \"method\": \"Lis1 mutant mouse embryonic fibroblasts, time-lapse live cell imaging, rescue experiments, immunofluorescence\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic mutant, epistasis rescue, live imaging, single lab\",\n      \"pmids\": [\"24030547\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Ndel1 and NudCL together regulate retrograde axonal mitochondrial transport. Knocking down both Ndel1 and NudCL almost blocks retrograde mitochondrial transport, while each alone only partially reduces it. LIS1 also interacts with KIF5b (kinesin) and its depletion suppresses mitochondrial motility in both anterograde and retrograde directions.\",\n      \"method\": \"siRNA knockdown (single and double), live imaging of mitochondrial transport in hippocampal neurons, co-immunoprecipitation\",\n      \"journal\": \"Traffic\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — double KD epistasis, live imaging quantification, single lab\",\n      \"pmids\": [\"23551859\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"NDEL1 localizes to the axon initial segment (AIS) via interaction with the scaffold protein Ankyrin-G. Depletion of NDEL1 or LIS1 results in non-polarized trafficking of dendritic cargo through the AIS. NDEL1 facilitates reversal of somatodendritic cargos in the proximal axon via local dynein activation.\",\n      \"method\": \"Co-immunoprecipitation, RNAi, live cargo tracking, immunofluorescence, fractionation\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, RNAi with live cargo tracking, defined localization mechanism, single lab multiple methods\",\n      \"pmids\": [\"26844830\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Ndel1 localizes to the subdistal appendage of the mother centriole and suppresses primary cilia formation in proliferating cells by maintaining trichoplein at the mother centriole, thereby sustaining Aurora A activation. Serum starvation induces transient Ndel1 degradation followed by trichoplein disappearance and cilia assembly. Ndel1 acts upstream of the trichoplein-Aurora A pathway.\",\n      \"method\": \"siRNA knockdown, forced expression, immunofluorescence, mouse genetics (Ndel1 hypomorphic mice), co-localization studies\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — epistasis via rescue experiments, in vivo mouse model, siRNA, multiple orthogonal approaches\",\n      \"pmids\": [\"26880200\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Ndel1 interacts with TRIO-associated repeat on actin (Tara), an actin-bundling protein. Loss of Ndel1 or Tara impairs cell migration. Tara overexpression induces accumulation of Ndel1 at the cell periphery co-localizing with F-actin. Co-expression of Ndel1 and Tara causes synergistic increase in F-actin and filopodia formation.\",\n      \"method\": \"Co-immunoprecipitation, RNAi, wound healing and Boyden chamber migration assays, immunofluorescence\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, RNAi with migration phenotype, synergy assay, single lab\",\n      \"pmids\": [\"27546710\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Crystal structure of DISC1 C-terminal tail in complex with Ndel1 binding domain was solved at high resolution. DISC1 regulates Ndel1 kinetochore attachment (but not centrosome localization) during mitosis. Disrupting DISC1/Ndel1 complex formation prolongs mitotic length and causes cell-cycle deficits in human cells and mouse cortical radial glia.\",\n      \"method\": \"X-ray crystallography, co-immunoprecipitation, live cell imaging, mouse in utero electroporation, human forebrain organoids, patient iPSCs\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure combined with functional validation in multiple systems (human cells, mouse, organoids, patient iPSCs)\",\n      \"pmids\": [\"29103808\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Crystal structure of AnkB in complex with Ndel1 C-terminal coiled-coil (CT-CC) region revealed a stable 5-helix bundle with 2:1 (Ndel1:AnkB) stoichiometry. AnkG is essential for Ndel1 accumulation at the AIS. Cargo sorting at the AIS is disrupted by a peptide designed to block the AnkG/Ndel1 complex.\",\n      \"method\": \"X-ray crystallography, co-immunoprecipitation, live cargo tracking, peptide competition assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure with functional validation (peptide disruption of cargo sorting), single lab\",\n      \"pmids\": [\"31889000\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"GSK-3β phosphorylates dynein intermediate chain (IC) at conserved residues S87/T88 (IC-1B) and S88/T89 (IC-2C) within the Ndel1-binding domain. This phosphorylation reduces IC interaction with Ndel1. Pharmacological or genetic inhibition of GSK-3β stimulates dynein motility.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, site-directed mutagenesis, in vitro phosphorylation assay, dynein motility assay\",\n      \"journal\": \"Traffic\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro phosphorylation, MS identification, mutagenesis, functional motility assay, single lab\",\n      \"pmids\": [\"26010407\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"DBZ (DISC1-binding zinc finger protein) hinders Ndel1 phosphorylation at Thr219 and Ser251. DBZ depletion or expression of double-phosphorylated Ndel1 impairs anterograde transport of Lis1 and DISC1 to neurite tips. This identifies a role for Ndel1 dual-phosphorylation state in regulating anterograde transport.\",\n      \"method\": \"RNAi, phosphomimetic expression, in utero electroporation, immunofluorescence, microtubule elongation assay\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — phosphomimetic mutants, in vivo electroporation, rescue experiments, single lab\",\n      \"pmids\": [\"25698733\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"NDEL1 is specifically S-nitrosylated at Cys203 by neuronal nitric oxide synthase (nNOS) in an NMDA receptor-activity-dependent manner. This S-nitrosylation accelerates dendritic arborization. Disruption of NDEL1 S-nitrosylation mediates impaired dendritic maturation caused by developmental alcohol exposure.\",\n      \"method\": \"Biotin-switch S-nitrosylation assay, site-directed mutagenesis of Cys203, genetic Nos1 deletion, NMDA receptor pharmacology, dendritic morphometry\",\n      \"journal\": \"Cerebral cortex\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct S-nitrosylation assay with site-specific mutant, genetic NOS1 KO, functional dendritic readout, single lab\",\n      \"pmids\": [\"27371763\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Ndel1 directly associates with Dynamin 2 (Dyn2) and enhances Dyn2 GTPase activity in its unassembled and assembled forms without promoting oligomerization. Gain and loss of function of Ndel1 recapitulate effects of Dyn2 overexpression or dominant-negative Dyn2 on intracellular localization of GluR1.\",\n      \"method\": \"Co-immunoprecipitation, in vitro GTPase activity assay, gain/loss-of-function experiments, GluR1 localization assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro GTPase assay, co-IP, gain/loss of function, single lab\",\n      \"pmids\": [\"21283621\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Ndel1 binds directly to keratin subunits through a motif conserved in all intermediate filament proteins and is necessary for robust desmosome-keratin association. Lis1 is required for desmosomal localization of Ndel1 but not for its effects on keratin filaments. Loss of Ndel1 in mouse epidermis results in desmosome defects.\",\n      \"method\": \"Direct binding assay, mouse genetics (conditional KO), immunofluorescence, desmosome morphology analysis\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding assay, mouse genetic KO with defined phenotype, mechanistic dissection of Lis1 role, single lab\",\n      \"pmids\": [\"34319758\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"The dynein intermediate chain N-terminus (ICN) is a critical evolutionarily conserved hub that interacts with both dynactin and Ndel1. Ndel1 recruits LIS1 to the dynein complex via ICN binding. LIS1 cannot simultaneously bind Ndel1 and dynein, requiring LIS1 to be handed off from Ndel1 to dynein in temporally discrete steps. In vitro, Ndel1 inhibits dynein activation by disfavoring dynein-dynactin-adaptor complex formation and by sequestering Lis1 away from dynein. Phosphomimetic C-terminal domain mutations in Ndel1 increase its ability to inhibit dynein-dynactin-adaptor complex formation.\",\n      \"method\": \"Purified protein binding assays, single-molecule imaging, in vitro reconstitution of dynein-dynactin-adaptor complex, mutagenesis\",\n      \"journal\": \"Nature communications / The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with purified components, single-molecule imaging, mutagenesis, replicated across two independent publications\",\n      \"pmids\": [\"37730751\", \"37086789\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The NDEL1 variant p.R105P disrupts NDEL1 binding to LIS1, impairs neuronal migration, increases leading process length, and disrupts nucleus-centrosome coupling (nucleokinesis). This identifies the critical role of the LIS1-binding interface of NDEL1 in nucleokinesis during cortical development.\",\n      \"method\": \"In utero electroporation (mouse), single-cell RNA sequencing, spatial transcriptomics, biochemical binding assay, patient variant analysis\",\n      \"journal\": \"Acta neuropathologica\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — disease variant functional validation in vivo, biochemical binding disruption, multiple orthogonal methods, single study\",\n      \"pmids\": [\"38194050\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NDEL1 is a multifunctional scaffold protein that directly binds LIS1, cytoplasmic dynein intermediate chain, and dynactin to regulate dynein activation; it recruits LIS1 to dynein through the intermediate chain N-terminus and must be released before LIS1 is handed off to dynein for processive transport. NDEL1 activity is regulated by multiple phosphorylation events (CDK5/CDK1 at Thr219/Ser251, Aurora-A at Ser251, Erk1/2) and additional modifications (palmitoylation at Cys-273 region, S-nitrosylation at Cys203) that modulate its interactions with dynein, LIS1, and other partners to control neuronal migration, nucleokinesis, centrosome maturation, ciliogenesis suppression, kinetochore function, axonal cargo selectivity at the AIS, and neurofilament assembly.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NDEL1 is a coiled-coil scaffold protein that functions as a central regulator of cytoplasmic dynein, controlling dynein recruitment and activation to drive neuronal migration, mitotic processes, and intracellular transport [#0, #4, #6]. It directly binds LIS1, the dynein intermediate chain, and dynactin, recruiting LIS1 to dynein through the conserved intermediate-chain N-terminus; because LIS1 cannot simultaneously occupy NDEL1 and dynein, NDEL1 must hand LIS1 off in discrete steps and is itself a negative regulator that disfavors dynein-dynactin-adaptor assembly until released [#14, #17, #49]. In neurons, NDEL1 acts cell-autonomously with LIS1 to couple the nucleus and centrosome during nucleokinesis, and its disruption underlies cortical migration defects, including the disease-associated p.R105P variant that ablates LIS1 binding [#4, #28, #50]. NDEL1 activity is gated by a dense layer of post-translational modification: CDK5/CDK1, Aurora-A, and Erk1/2 phosphorylation, palmitoylation, and S-nitrosylation each remodel its affinity for dynein, LIS1, and partner proteins to switch transport on or off in distinct compartments [#5, #8, #22, #23, #29, #46]. Beyond dynein, NDEL1 organizes the centrosome and mother centriole, suppresses ciliogenesis through the trichoplein-Aurora A pathway, supports kinetochore dynein function, and bridges DISC1 into a DISC1-NDEL1-LIS1 complex relevant to neurite extension [#3, #16, #40, #10]. It additionally engages cytoskeletal and signaling systems—neurofilament and keratin intermediate filaments, the WAVE regulatory complex, Cdc42GAP, and intermediate-filament transport—and possesses an intrinsic Cys273-dependent endooligopeptidase activity required for neurite outgrowth [#13, #36, #20, #30, #48].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Established NDEL1 as a LIS1 partner and CDK5 substrate at centrosomes and growth cones, linking it to dynein and neuronal morphology and seeding the entire dynein-regulation model.\",\n      \"evidence\": \"Co-IP, subcellular fractionation, in vitro kinase assay and immunofluorescence in neurons\",\n      \"pmids\": [\"11163260\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define how phosphorylation alters dynein binding\", \"No structural basis for LIS1 interaction\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Identified DISC1 as an NDEL1 binding partner whose disease-truncation abolishes binding, connecting NDEL1 to a psychiatric-disease pathway and neurite extension.\",\n      \"evidence\": \"Yeast two-hybrid, Co-IP and neurite outgrowth in PC12 cells\",\n      \"pmids\": [\"12506198\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Binding interface not mapped\", \"Functional consequence beyond neurite length unknown\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Mapped the DISC1-NDEL1-LIS1 trimolecular architecture and showed NDEL1 phosphorylation by CDK1/Erk1/2 and 14-3-3epsilon binding control its localization and LIS1 association, establishing NDEL1 as a phospho-regulated bridge.\",\n      \"evidence\": \"Two-hybrid and deletion mapping, in vitro kinase assays with phospho-mutants, mouse Ywhae genetics\",\n      \"pmids\": [\"12812986\", \"14962739\", \"12556484\", \"12796778\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry of the trimolecular complex unresolved\", \"How 14-3-3 binding mechanistically stabilizes phosphorylation unclear\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Demonstrated NDEL1 acts upstream of dynein and in a common pathway with LIS1, directly binding dynein heavy chain to drive membrane/organelle transport and nucleus-centrosome coupling.\",\n      \"evidence\": \"In utero RNAi with LIS1 rescue epistasis, dynein/LIS1-binding mutants, lysosome motility time-lapse, neurofilament binding and polymerization assays\",\n      \"pmids\": [\"15473966\", \"14970193\", \"15208636\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether NDEL1 activates or recruits dynein not yet distinguished\", \"Direct vs indirect effects on motor processivity untested\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Revealed NDEL1 as a multifunctional effector—targeting dynein to microtubule plus ends via LIS1, linking CDK5 phosphorylation to katanin p60 distribution, and possessing intrinsic Cys273 endooligopeptidase activity inhibited by DISC1.\",\n      \"evidence\": \"Yeast null genetics with live imaging, Co-IP and migration assays, active-site mutagenesis with enzymatic and competitive-inhibition assays, knockout mouse\",\n      \"pmids\": [\"15965467\", \"16203747\", \"15728732\", \"16107726\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological substrates of the peptidase activity unidentified\", \"Relationship between scaffolding and enzymatic functions unclear\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Placed NDEL1 in mitotic centrosome control, showing Aurora-A phosphorylation at Ser251 and direct TACC3 interaction drive centrosome maturation and separation.\",\n      \"evidence\": \"In vitro kinase assay, phosphomimetic rescue of Aurora-A depletion, Co-IP and immunofluorescence\",\n      \"pmids\": [\"17060449\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How Ser251 phosphorylation alters dynein/LIS1 binding not defined\", \"TACC3 recruitment mechanism incomplete\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Defined NDEL1 kinetochore function—recruited via CENP-F to stabilize dynein/dynactin and ensure chromosome alignment—and solved the coiled-coil homodimer structure rationalizing cooperative LIS1 binding.\",\n      \"evidence\": \"Co-IP, siRNA with live imaging of chromosome behavior, X-ray crystallography of residues 10-166\",\n      \"pmids\": [\"17600710\", \"17494871\", \"17997972\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"C-terminal cargo/dynein region not crystallized\", \"Distinct roles of NDEL1 vs NDE1 at kinetochores not fully separated\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Resolved how NDEL1 phosphorylation is reversed and broadened its reach, showing PP4c dephosphorylates CDK1 sites to limit katanin recruitment, NDEL1 functions in prophase nuclear-envelope invagination, and it controls Cdc42 signaling, PDE4/cAMP scaffolding, and vimentin transport.\",\n      \"evidence\": \"In vitro phosphatase assay with genetic/pharmacological epistasis, siRNA with live imaging, competitive Cdc42GAP binding and migration assays, BRET and TAP-MS\",\n      \"pmids\": [\"18347064\", \"18809722\", \"18331715\", \"18845247\", \"18303022\", \"18784752\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Integration of these parallel functions in a single cell unclear\", \"How LIS1 blocking of dynein is relieved mechanistically not fully defined\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Established palmitoylation at the Cys273 region as a switch reducing dynein binding, defined NDEL1's role in retrograde axonal transport and adhesion dynamics, and placed it in an aPKC-Aurora-A-TPX2 cascade driving neurite microtubule emanation.\",\n      \"evidence\": \"Metabolic palmitoylation labeling with transport assays, antibody-blocking in DRG axons, paxillin/FAK Co-IP and adhesion assays, in vitro kinase and live MT imaging\",\n      \"pmids\": [\"19927128\", \"19522757\", \"19492042\", \"19668197\", \"17202468\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Palmitoylating enzyme(s) not identified\", \"Crosstalk between palmitoylation and phosphorylation untested\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Positioned NDE1/NDEL1 upstream of LIS1 for membrane dynein recruitment, identified an N-terminal dynein-IC binding domain and lamin-B-dependent spindle matrix role, and rescued PDE-driven defects, consolidating NDEL1 as the membrane dynein adaptor.\",\n      \"evidence\": \"Double siRNA epistasis with membrane fractionation, Xenopus extract spindle reconstitution with mutagenesis, neurite-outgrowth rescue with catalytic mutant\",\n      \"pmids\": [\"20048338\", \"19198602\", \"21056974\", \"20462516\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How NDEL1/NDE1 associate with membranes molecularly unclear\", \"Endopeptidase substrate during neurite outgrowth unknown\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Defined the phosphorylation-gated motility switch: CDK5-phosphorylated NDEL1 forms a high-affinity LIS1/NDEL1/dynein complex that blocks ATP-dependent dynein release, and uncovered Dynamin 2 GTPase regulation, centrosomal microtubule anchoring, and additional partner contexts.\",\n      \"evidence\": \"Phospho-mutants and RNAi with axonal transport assays, in vitro GTPase assay, mutant mapping of centrosome targeting\",\n      \"pmids\": [\"22114287\", \"26166569\", \"21283621\", \"16291865\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Reconciliation of inhibitory vs activating roles across cell types incomplete\", \"Quantitative kinetics of LIS1 handoff not yet measured\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Determined NDEL1's higher-order architecture (dimers/tetramers/folded-back polymers) and expanded its functions to protein quality control (misfolded Gβ to aggresome) and WAVE regulatory complex assembly for actin polymerization.\",\n      \"evidence\": \"Negative-stain EM and crosslinking-MS, Co-IP and aggresome/half-life assays, in vitro actin polymerization and cell-spreading assays\",\n      \"pmids\": [\"22843697\", \"22430153\", \"22453242\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional significance of polymeric self-assembly in cells unclear\", \"How NDEL1 selects misfolded clients undefined\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Placed NDEL1-dynein downstream of LIS1 for mitotic spindle orientation and showed cooperation with NudCL in retrograde mitochondrial transport.\",\n      \"evidence\": \"Lis1-mutant MEFs with rescue and live imaging, double siRNA with mitochondrial transport imaging and Co-IP\",\n      \"pmids\": [\"24030547\", \"23551859\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs indirect role of NDEL1 in spindle orientation not isolated\", \"Mechanism of NudCL cooperation unclear\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identified NDEL1's localization-based control of cargo polarity at the AIS via Ankyrin-G and its suppression of ciliogenesis through trichoplein-Aurora A, plus actin-bundling cooperation with Tara.\",\n      \"evidence\": \"Co-IP and live cargo tracking with fractionation, siRNA and hypomorphic mouse with co-localization, migration and synergy assays\",\n      \"pmids\": [\"26844830\", \"26880200\", \"27546710\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How AnkG recruitment couples to local dynein activation incompletely defined\", \"Trigger for serum-starvation-induced NDEL1 degradation unknown\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Provided structural and functional resolution of the DISC1-NDEL1 interface, linking it specifically to NDEL1 kinetochore attachment and mitotic timing in human cells, organoids, and patient iPSCs, and showed nNOS S-nitrosylation of Cys203 promotes dendritic arborization.\",\n      \"evidence\": \"X-ray crystallography with multi-system functional validation, biotin-switch S-nitrosylation assay with Cys203 mutant and Nos1 deletion\",\n      \"pmids\": [\"29103808\", \"27371763\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether S-nitrosylation intersects with dynein regulation untested\", \"Interplay of DISC1-controlled kinetochore role with neuronal functions unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Solved the AnkB-NDEL1 5-helix bundle structure (2:1 stoichiometry) and demonstrated that disrupting the AnkG/NDEL1 complex disrupts AIS cargo sorting, cementing the structural basis of NDEL1 AIS recruitment.\",\n      \"evidence\": \"X-ray crystallography, Co-IP, live cargo tracking and peptide competition\",\n      \"pmids\": [\"31889000\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo requirement of this interface not tested\", \"Link between ankyrin binding and dynein activation incomplete\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Extended NDEL1's intermediate-filament role to keratins and desmosomes in epidermis, showing direct binding via a conserved IF motif and LIS1-dependent desmosomal localization.\",\n      \"evidence\": \"Direct binding assay, conditional knockout mouse with desmosome morphology analysis\",\n      \"pmids\": [\"34319758\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single-lab finding without independent replication\", \"Whether keratin/neurofilament binding share a common mechanism untested\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Reconstituted the mechanism with purified components: NDEL1 binds the conserved dynein IC N-terminus to recruit LIS1, but because LIS1 cannot bind NDEL1 and dynein simultaneously it must be handed off in discrete steps, and NDEL1 inhibits dynein-dynactin-adaptor assembly—an effect strengthened by phosphomimetic C-terminal mutations.\",\n      \"evidence\": \"Purified-protein binding, single-molecule imaging, in vitro dynein-dynactin-adaptor reconstitution and mutagenesis across two studies\",\n      \"pmids\": [\"37730751\", \"37086789\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Trigger that releases NDEL1 to permit handoff in cells unknown\", \"How phosphorylation timing is coordinated with cargo loading unresolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Provided direct disease causality, showing the p.R105P variant disrupts the NDEL1-LIS1 interface, impairs migration and nucleokinesis, validating the LIS1-binding interface as critical for cortical development.\",\n      \"evidence\": \"In utero electroporation, scRNA-seq and spatial transcriptomics, biochemical binding disruption, patient variant analysis\",\n      \"pmids\": [\"38194050\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full clinical spectrum of NDEL1 variants not defined\", \"Whether other NDEL1 interfaces contribute to disease untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the dense array of NDEL1 modifications and binding partners is coordinated spatiotemporally to switch between dynein inhibition and activation in a given cell remains the central open question.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No unified model integrating phosphorylation, palmitoylation, and S-nitrosylation timing\", \"In-cell trigger for LIS1 handoff from NDEL1 to dynein unidentified\", \"Physiological substrates of the endooligopeptidase activity unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [13, 14, 48, 21]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3, 4, 14, 49, 26]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [17, 49, 20, 47]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [30, 31]},\n      {\"term_id\": \"GO:0016787\", \"supporting_discovery_ids\": [30, 31]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 16, 40]},\n      {\"term_id\": \"GO:0005813\", \"supporting_discovery_ids\": [0, 16, 40]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 14, 26]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [10, 11, 42]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [20, 24, 39, 43]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [14, 26, 39, 49]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [4, 6, 28, 50]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [5, 8, 10, 37]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [14, 23, 25, 26]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [16, 40]}\n    ],\n    \"complexes\": [\n      \"LIS1-NDEL1-dynein complex\",\n      \"DISC1-NDEL1-LIS1 complex\",\n      \"WAVE regulatory complex (WRC)\",\n      \"dynein-dynactin-adaptor complex\"\n    ],\n    \"partners\": [\n      \"LIS1\",\n      \"DISC1\",\n      \"dynein intermediate chain\",\n      \"TACC3\",\n      \"CENP-F\",\n      \"katanin p60\",\n      \"Ankyrin-G\",\n      \"14-3-3epsilon\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}