Affinage

KIDINS220

Kinase D-interacting substrate of 220 kDa · UniProt Q9ULH0

Length
1771 aa
Mass
196.5 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Kidins220 (kinase D-interacting substrate of 220 kDa, also called ARMS) is an integral membrane scaffold protein, concentrated at neurite tips and lipid raft microdomains, that organizes multiple receptor signaling pathways to control neuronal survival, polarity, and synaptic function (PMID:10998417, PMID:15096499). It was first defined as the principal physiological substrate of Protein Kinase D, which phosphorylates it on Ser919 within a PKD consensus motif (PMID:10998417). Kidins220 is delivered to neurite tips as a kinesin-1 cargo through a KLC1-interacting motif, a transport step required for NGF-induced MAPK signaling and neurite outgrowth (PMID:17079733). As a membrane-anchored platform for the neurotrophin receptors TrkA/B/C and p75NTR and for VEGFR2, it couples these receptors to MAPK/ERK and PI3K/Akt signaling, and its loss in mice produces cardiovascular defects, neuronal apoptosis, and early postnatal death (PMID:22048155, PMID:22048169). Kidins220 promotes neurite extension by binding the RhoGEF Trio through its ankyrin repeats to drive Rac1 activation (PMID:20519585), and shapes dendritic arbor complexity and spine stability via TrkB/EphB2 receptor clustering and downstream PI3K/Akt signaling (PMID:19449316, PMID:22699907). At synapses it interacts with the NMDAR, AMPAR subunit GluA1, and voltage-gated sodium channels to tune excitatory transmission, plasticity, and excitability (PMID:19759287, PMID:20547223, PMID:26037926), and it negatively regulates BDNF secretion through control of Synaptotagmin-IV (PMID:29769266). Kidins220 is negatively regulated by activity-dependent calpain cleavage downstream of NMDAR overactivation, with the major cut site mapped between residues 1669 and 1670; this proteolysis governs synaptic plasticity and neuronal viability during excitotoxicity and is modulated by a GSK3β/PP1 phosphorylation balance (PMID:19759287, PMID:20943655, PMID:23118350, PMID:26492372). Beyond the nervous system, Kidins220 couples antigen receptors to downstream signaling—linking the TCR to B-Raf for sustained ERK activation and the BCR to PLCγ2/Ca2+/ERK (PMID:23359496, PMID:26324445)—and acts as an obligate partner of the phosphate exporter XPR1 to maintain phosphate homeostasis (PMID:35437317) and of the SNX27-retromer to preserve surface AQP4 and CSF homeostasis (PMID:34002021). A homozygous in-frame KIDINS220 deletion that weakens TrkA binding causes fetal ventriculomegaly with limb contractures, establishing a Mendelian disease link (PMID:33205811).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2000 High

    Established Kidins220's founding biochemical identity by showing it is the first physiological PKD substrate, defining a specific regulated phosphorylation event (Ser919) that links it to PKD signaling.

    Evidence Co-IP, in vitro kinase assays with constitutively active/dominant-negative PKD, S919A mutagenesis, and phospho-specific antibody in PC12 cells

    PMID:10998417

    Open questions at the time
    • Functional consequence of S919 phosphorylation on scaffold behavior not resolved
    • Domain analysis (11 ankyrin repeats, 4 TM domains) descriptive, not functionally dissected
  2. 2004 Medium

    Connected Kidins220 localization to lipid raft microdomains and showed raft integrity governs its PKD-dependent phosphorylation and its polarized membrane positioning in motile cells.

    Evidence Sucrose gradient fractionation, live GFP-PKD imaging, methyl-β-cyclodextrin raft disruption in neurons; immunocytochemistry and motility assays in dendritic cells

    PMID:14971036 PMID:15096499

    Open questions at the time
    • Molecular basis of raft targeting not defined
    • Link between raft localization and downstream scaffold output incomplete
  3. 2006 High

    Explained how Kidins220 reaches its functional site by identifying it as a KLC1-dependent kinesin-1 cargo, coupling axonal transport to NGF-MAPK signaling and neurite outgrowth.

    Evidence Yeast two-hybrid, GST-pulldown, co-IP, live imaging, and dominant-negative KIM overexpression in PC12 cells

    PMID:17079733

    Open questions at the time
    • Regulation of cargo loading/unloading unknown
    • Whether transport is activity- or phosphorylation-dependent untested
  4. 2009 High

    Defined Kidins220 as a cytoskeletal and GEF-linked organizer of neuronal polarity, binding tubulin/MAPs and the RhoGEF Trio to drive Rac1-dependent neurite extension and proper axon/dendrite specification.

    Evidence Co-IP, GST-pulldown, shRNA/overexpression in hippocampal neurons, dominant-negative ankyrin-repeat experiments, neurite outgrowth assays

    PMID:19903810 PMID:20519585

    Open questions at the time
    • How Trio activity is regulated within the complex not resolved
    • Direct effect on microtubule dynamics inferred from phosphorylation changes only
  5. 2009 High

    Established Kidins220 as an NMDAR-associated survival factor that is selectively degraded during excitotoxicity through calpain cleavage and transcriptional silencing.

    Evidence Co-IP, calpain inhibitor and Ca2+ chelation experiments, shRNA, ERK and viability assays, in vivo ischemia model

    PMID:19759287

    Open questions at the time
    • Calpain cleavage site not yet mapped at this stage
    • Mechanism of transcriptional silencing unknown
  6. 2009 Medium

    Demonstrated in vivo that Kidins220 stabilizes (rather than forms) dendritic arbors and cortical spines, distinguishing a maintenance role.

    Evidence Two-photon imaging and Golgi staining in heterozygous knockout mice

    PMID:19449316

    Open questions at the time
    • Molecular effectors of spine stabilization not identified here
    • Heterozygous model may underrepresent full loss
  7. 2010 Medium

    Positioned Kidins220 as a regulator of synaptic transmission and plasticity, negatively modulating AMPAR (GluA1) function and tuning LTP through calpain-mediated activity-dependent proteolysis.

    Evidence Electrophysiology in hippocampal slices, co-IP with GluA1, surface biotinylation, KCl depolarization with calpain inhibition in knockout mice

    PMID:20547223 PMID:20943655

    Open questions at the time
    • Direct vs indirect effect on GluA1 trafficking unresolved
    • Calpain site still unmapped at this point
  8. 2011 High

    Defined Kidins220 as an essential scaffold for VEGFR2 and neurotrophin (Trk/p75NTR) receptors in vivo, required for cardiovascular development and central/peripheral neuronal survival.

    Evidence Co-IP, full and conditional knockout mouse phenotyping, MAPK assays, electrophysiology, TUNEL and IHC

    PMID:22048155 PMID:22048169

    Open questions at the time
    • Receptor-specific contributions to lethality not separated
    • Stoichiometry of multi-receptor scaffolding unknown
  9. 2012 Medium

    Extended Kidins220's synaptic role to GABAergic short-term plasticity and inhibitory transmission and linked its calpain clearance to a GSK3β/PP1 balance relevant to Alzheimer pathology.

    Evidence Patch-clamp in knockout cultures; immunoblotting in AD brain and GSK3β-transgenic mice with in vitro calpain proteolysis assays

    PMID:22563401 PMID:23118350

    Open questions at the time
    • GABAergic vesicle-release mechanism downstream of Kidins220 not defined
    • AD association correlative, not causal
  10. 2013 High

    Showed Kidins220 also controls dendritic branching via PI3K/Akt downstream of TrkB and EphB2, with receptor overexpression rescuing loss-of-function defects.

    Evidence In utero electroporation, shRNA, TrkB/EphB2 rescue, PI3K/Akt inhibitors, receptor clustering assays

    PMID:22699907

    Open questions at the time
    • How Kidins220 promotes EphB2 complex clustering mechanistically unclear
  11. 2015 High

    Mapped the major calpain cleavage site (aa 1669/1670) and used a protective peptide to validate that blocking cleavage preserves ERK/CREB signaling and neuronal viability; concurrently identified Kidins220 as a modulator of Nav channels.

    Evidence Cleavage mapping with truncations, Tat-K cell-penetrating peptide rescue; co-IP with Nav and patch-clamp in knockout neurons and HEK293

    PMID:26037926 PMID:26492372

    Open questions at the time
    • Whether Nav modulation is direct or scaffold-mediated unresolved
    • Therapeutic translatability of protective peptide untested in vivo broadly
  12. 2013 High

    Extended Kidins220 scaffolding to immune receptor signaling, coupling the TCR to B-Raf for sustained ERK activation.

    Evidence Mass spectrometry, co-IP, proximity ligation, shRNA in T cell lines, Ca2+ imaging, ERK time-course, cytokine readouts

    PMID:23359496

    Open questions at the time
    • Mechanism distinguishing sustained vs transient ERK coupling not fully defined
  13. 2015 High

    Established Kidins220 as a BCR-associated scaffold coupling antigen receptor engagement to PLCγ2/Ca2+/ERK and required for normal B cell development.

    Evidence Mass spectrometry, co-IP, B cell-specific conditional knockout, PLCγ2/Ca2+/ERK assays, FACS

    PMID:26324445

    Open questions at the time
    • Direct binding interface with BCR components not mapped
    • Src-independent recruitment mechanism unexplained
  14. 2018 Medium

    Identified a presynaptic-secretory role: Kidins220 negatively regulates regulated BDNF secretion via Synaptotagmin-IV, with relevance to Huntington's disease BDNF deficits.

    Evidence Conditional knockout, BDNF secretion assays, Syt-IV measurement, HD mouse models and human HD brain immunoblotting

    PMID:29769266

    Open questions at the time
    • Mechanism linking Kidins220 to Syt-IV levels not deeply validated
  15. 2019 Medium

    Revealed a glial function: Kidins220 in astrocytes maintains Ca2+ signaling (store-operated entry, TRPV4 levels), stress resistance, and supports neuronal connectivity.

    Evidence Ca2+ imaging, TRPV4 immunoblotting/IF, genotoxic stress assays, and neuron co-culture in knockout astrocytes

    PMID:31624352

    Open questions at the time
    • Mechanism of TRPV4 overexpression upon Kidins220 loss unknown
    • Direct Ca2+-channel partners in astrocytes not identified
  16. 2021 High

    Defined two non-neuronal scaffold functions and a human disease link: Kidins220 maintains surface AQP4 via the SNX27-retromer to control CSF/ventricular homeostasis, and a TrkA-binding-deficient KIDINS220 deletion causes fetal ventriculomegaly with limb contractures.

    Evidence Knockout mouse phenotyping, SNX27 knockdown/rescue, lysosomal inhibition, patient tissue; co-IP of mutant vs WT with TrkA, exome sequencing and fetal imaging

    PMID:33205811 PMID:34002021

    Open questions at the time
    • How Kidins220 stabilizes SNX27-retromer levels mechanistically unclear
    • Causality of single human deletion family limited
  17. 2022 High

    Established Kidins220 as an obligate partner of the phosphate exporter XPR1, required for XPR1 localization and activity, with therapeutic implications for phosphate-stressed cancers.

    Evidence CRISPR loss-of-function screens, localization and phosphate efflux assays, vacuolar imaging, and xenografts

    PMID:35437317

    Open questions at the time
    • Structural basis of XPR1-Kidins220 complex not resolved
    • Whether neuronal Kidins220 roles intersect with phosphate handling unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single scaffold integrates and prioritizes its many receptor and transporter partners (neurotrophin/VEGFR2, antigen receptors, ion channels, XPR1, SNX27-retromer) in a context-specific manner remains unresolved.
  • No structural model of multi-partner assembly
  • Phosphorylation/proteolysis code that switches between functions not defined
  • Tissue-specific partner selection unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-112316 Neuronal System 4 R-HSA-168256 Immune System 2 R-HSA-382551 Transport of small molecules 2 R-HSA-9609507 Protein localization 2
Partners
BRAFKLC1NTRK1PRKD1SNX27TRIOVEGFR2XPR1
Complex memberships
SNX27-retromerXPR1-KIDINS220 complexkinesin-1 (KLC1) complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Kidins220 was identified as the first physiological substrate of Protein Kinase D (PKD). PKD co-immunoprecipitates and phosphorylates endogenous Kidins220 in PC12 cells. A constitutively active PKD mutant (PKD-S744E/S748E) phosphorylates recombinant Kidins220 in vitro, while a dominant-negative PKD mutant (PKD-D733A) abolishes this phosphorylation. The specific phosphorylation site was mapped to serine 919 within a PKD consensus motif; substitution of S919 to alanine abrogated phosphorylation. Phorbol ester treatment causes specific phosphorylation of S919 in vivo. Co-immunoprecipitation, in vitro kinase assay with constitutively active and dominant-negative PKD mutants, site-directed mutagenesis (S919A), phospho-specific antibody, phorbol ester stimulation in PC12 cells The Journal of biological chemistry High 10998417
2000 Kidins220 is an integral membrane protein with 11 ankyrin repeats and four transmembrane domains, selectively expressed in brain and neuroendocrine cells, where it concentrates at the tip of neurites. Cloning, domain analysis, subcellular fractionation, immunocytochemistry in PC12 cells The Journal of biological chemistry Medium 10998417
2004 Kidins220 is constitutively associated with lipid rafts in PC12 cells, primary cortical neurons, and brain synaptosomes. Cholesterol depletion with methyl-β-cyclodextrin alters Kidins220 localization and detergent solubility and delays PKD translocation to lipid raft microdomains. Lipid raft disruption activates PKD and increases Kidins220 phosphorylation on Ser919 via a mechanism involving PKCε and Src kinase. Sucrose gradient fractionation, immunocytochemistry, confocal microscopy, live-cell GFP-PKD translocation imaging, methyl-β-cyclodextrin cholesterol depletion The Journal of biological chemistry Medium 15096499
2006 Kidins220 interacts with the kinesin-1 motor complex via kinesin light chain 1 (KLC1). The interaction was identified by yeast two-hybrid screen and confirmed by GST-pulldown and co-immunoprecipitation. The interaction maps to a short KLC-interacting motif (KIM) in Kidins220 requiring both the TPR and heptad repeat regions of KLC1. Overexpression of KIM in differentiating PC12 cells impairs transport of EGFP-Kidins220 carriers to neurite tips and inhibits NGF-induced MAPK signaling and neurite outgrowth. Yeast two-hybrid, GST-pulldown, co-immunoprecipitation, live-cell fluorescence imaging, KIM overexpression dominant-negative experiment, MAPK signaling assay Molecular biology of the cell High 17079733
2007 PKD1, PKD2, and Kidins220 co-exist with neurotensin (NT)-containing vesicles in BON endocrine cells. shRNA-mediated knockdown of Kidins220 inhibits NT secretion. Overexpression of kinase-dead PKD1 abrogates Kidins220 expression and NT vesicle formation, establishing a PKD/Kidins220 pathway in regulation of hormone secretion. Co-immunoprecipitation, shRNA knockdown, immunofluorescence co-localization, dominant-negative PKD1 overexpression, NT secretion assay The Journal of biological chemistry Medium 18048355
2009 Kidins220 is downregulated in excitotoxicity via two mechanisms: (1) rapid calpain-mediated cleavage triggered by NR2B-containing NMDAR overactivation and Ca2+ influx, and (2) calpain-independent transcriptional silencing of the Kidins220/Arms gene. Kidins220 forms a complex with NMDARs. Kidins220 knockdown decreases ERK activation and basal neuronal viability, and enhances neuronal death under excitotoxic conditions. Co-immunoprecipitation (Kidins220-NMDAR association), calpain inhibitor experiments, Ca2+ chelation, shRNA knockdown, ERK phosphorylation assay, neuronal viability assay, in vivo cerebral ischemia model Journal of cell science High 19759287
2009 Kidins220 modulates neuronal polarity and dendritic development by interacting with tubulin and microtubule-regulating proteins including MAP1a, MAP1b, MAP2, and two stathmin family members. Knockdown of Kidins220 results in multiple axon-like extensions and aberrant dendritic arbors, and alters phosphorylation of MAP1b and stathmins. Co-immunoprecipitation (Kidins220 with tubulin and MAPs), shRNA knockdown and overexpression in hippocampal neurons, phosphorylation assays, immunocytochemistry The Journal of biological chemistry Medium 19903810
2009 ARMS/Kidins220 regulates dendritic arbor complexity and spine stability in vivo. In ARMS/Kidins220(+/-) mice, dendritic complexity decreases in young adults (not adolescents), and the rate of cortical spine elimination is elevated at 1 month of age, indicating a role in stabilization rather than initial formation of dendritic structures. In vivo two-photon imaging of cortical spines, Golgi staining of dendritic arbors in heterozygous knockout mice Developmental neurobiology Medium 19449316
2010 Kidins220 directly interacts with the RhoGEF Trio through the N-terminus of Trio and the ankyrin repeats of Kidins220. Trio and Kidins220 co-localize at neurite tips in NGF-differentiated PC12 cells along with F-actin and Rac1. Expression of the ankyrin repeats of Kidins220 (dominant negative) inhibits NGF-dependent and Trio-induced neurite outgrowth in PC12 cells and primary hippocampal neurons, placing Kidins220 upstream of Rac1 activation in neurite extension. Co-immunoprecipitation, GST-pulldown (direct interaction), co-localization by confocal microscopy, dominant-negative ankyrin repeat overexpression, neurite outgrowth assay Journal of cell science High 20519585
2010 ARMS/Kidins220 levels regulate basal synaptic transmission in hippocampal neurons. Decreased ARMS/Kidins220 in vivo increased basal synaptic transmission without affecting paired-pulse facilitation. ARMS/Kidins220 interacts with the AMPA receptor subunit GluA1 by co-immunoprecipitation, and modulates GluA1 phosphorylation and cell-surface localization. ARMS/Kidins220 acts as a negative regulator of AMPAR function as shown by inward rectification assays. Electrophysiology (field recordings in hippocampal slices), co-immunoprecipitation (Kidins220-GluA1), shRNA knockdown, cell-surface biotinylation, inward rectification assay Molecular and cellular neurosciences Medium 20547223
2010 ARMS/Kidins220 is cleaved by calpain in an activity-dependent manner following KCl depolarization in hippocampal neurons. ARMS/Kidins220(+/-) mice exhibit enhanced long-term potentiation, and calpain inhibition reverses this effect, indicating that calpain-mediated proteolysis of ARMS/Kidins220 regulates synaptic plasticity. KCl depolarization of hippocampal neurons, calpain inhibitor experiments, LTP recordings in hippocampal slices from heterozygous knockout mice The Journal of biological chemistry Medium 20943655
2011 Kidins220 constitutively interacts with VEGFR2 and mediates VEGF signaling. Kidins220(-/-) embryos display cardiovascular abnormalities and extensive neuronal apoptosis. Primary neurons from Kidins220(-/-) mice show reduced MAPK signaling, neurite outgrowth, and potentiation of excitatory postsynaptic currents in response to BDNF. Co-immunoprecipitation (Kidins220-VEGFR2), full knockout mouse phenotyping, MAPK phosphorylation assay in primary neurons, whole-cell electrophysiology, neurite outgrowth assay Cell death and differentiation High 22048155
2011 Kidins220 is required for heart outflow tract and ventricle wall development, and for peripheral nervous system (DRG) survival. Neuronal-specific deletion of Kidins220 leads to early postnatal death. Kidins220 functions as a membrane-anchored scaffold for neurotrophin receptors TrkA/B/C and p75NTR. Full and conditional knockout mouse histology, apoptosis assays (TUNEL), immunohistochemistry for Trk and p75NTR Cell death & disease Medium 22048169
2012 Kidins220 accumulates with hyperphosphorylated tau in Alzheimer's disease brains. GSK3β phosphorylation of Kidins220 decreases its susceptibility to calpain-mediated proteolysis, while PP1 action has the opposite effect, establishing a GSK3β/PP1 imbalance as a mechanism controlling Kidins220 clearance in neurodegeneration. Immunoprecipitation and immunoblotting in AD brain necropsies and GSK3β-transgenic mice, in vitro calpain proteolysis assays, kinase/phosphatase treatment experiments Human molecular genetics Medium 23118350
2012 Kidins220/ARMS is a novel modulator of short-term synaptic plasticity specifically in GABAergic neurons. In Kidins220(-/-) hippocampal neurons, the slow recovery from synaptic depression of inhibitory postsynaptic currents is strongly reduced. This phenotype is explained by absence of a transient reduction in vesicle release probability that occurs in wild-type GABAergic synapses. Whole-cell patch-clamp recordings (paired-pulse and train stimulation protocols) in Kidins220 full knockout hippocampal cultures PloS one Medium 22563401
2012 ARMS/Kidins220 knockdown impairs dendritic branching in mouse cerebral cortex in vivo and reduces dendritic length, number, and complexity in primary hippocampal neurons. Overexpression of TrkB or EphB2 in ARMS/Kidins220-deficient neurons partially rescues dendritic defects. PI3K/Akt signaling is a key downstream pathway; loss of ARMS/Kidins220 reduces EphB2 receptor signaling complex clustering. In utero electroporation for in vivo knockdown, shRNA in primary neurons, TrkB/EphB2 overexpression rescue, PI3K/Akt inhibitors, receptor clustering assays The Journal of neuroscience High 22699907
2013 Kidins220 associates with the pre-TCR, αβTCR, and γδTCR, and with B-Raf. Kidins220 is required for TCR-induced sustained (but not transient) Erk activation and optimal calcium signaling. Upon prolonged TCR stimulation, the Kidins220-TCR interaction decreases. Loss of Kidins220 blocks induction of c-Fos and Egr-1 and reduces CD69, IL-2, and IFN-γ upregulation, placing Kidins220 as a coupler of B-Raf to the TCR for sustained Erk signaling. Mass spectrometry identification of B-Raf interaction, co-immunoprecipitation, proximity ligation assay, shRNA knockdown in T cell lines, intracellular calcium imaging, ERK phosphorylation time-course assays, cytokine measurement Journal of immunology High 23359496
2015 The major calpain cleavage site in Kidins220 was mapped to between amino acids 1669 and 1670 in a highly conserved C-terminal sequence. A cell-penetrating peptide (Tat-K) encompassing this site (aa 1668–1681) reduces Kidins220 calpain processing dose- and time-dependently after excitotoxic insult, preserves pERK1/2 and pCREB activity, and increases neuronal viability. In vitro and in vivo calpain cleavage assays with deletion/truncation mapping, cell-penetrating peptide transduction, ERK and CREB phosphorylation assays, neuronal viability assay Cell death & disease Medium 26492372
2015 Kidins220 associates with brain voltage-gated sodium channels (Nav) as shown by co-immunoprecipitation. Kidins220 ablation increases excitability of hippocampal GABAergic neurons, increases sodium conductance, and alters Nav current kinetics and voltage dependence in HEK293 cells co-transfected with Nav channels, placing Kidins220 as a modulator of Nav channel activity. Co-immunoprecipitation (Kidins220-Nav), multielectrode array recordings, current-clamp recordings, patch-clamp Nav current recordings in HEK293 cells, in silico neuronal model The Journal of biological chemistry High 26037926
2015 Kidins220/ARMS binds to the B cell antigen receptor (BCR) complex in both resting and stimulated states; upon BCR stimulation, this interaction increases in a Src kinase-independent manner. Kidins220 couples the BCR to PLCγ2, Ca2+, and ERK signaling. Conditional B cell-specific knockout (B-KO) shows impaired pre-BCR and BCR signaling, reduced B cell activation, and a sixfold reduction in λ light chain-positive B cells, genetically placing Kidins220 in the PLCγ2 pathway. Mass spectrometry identification, co-immunoprecipitation, conditional knockout mouse (B cell-specific Cre), PLCγ2/Ca2+/ERK signaling assays, B cell development FACS analysis The Journal of experimental medicine High 26324445
2018 ARMS/Kidins220 negatively regulates regulated BDNF secretion in neurons. Downregulation of ARMS/Kidins220 in adult mouse brain increases BDNF secretion and striatal BDNF accumulation. In two mouse models of Huntington's disease, ARMS/Kidins220 is elevated in the hippocampus and regulated BDNF secretion is impaired; reducing ARMS/Kidins220 reverses this defect. ARMS/Kidins220 regulates Synaptotagmin-IV (Syt-IV) levels, which modulates BDNF secretion. Conditional mouse knockout for ARMS/Kidins220, BDNF secretion assays in neurons and hippocampal slices, Syt-IV protein level measurement, HD transgenic mouse models, human HD brain immunoblotting The Journal of neuroscience Medium 29769266
2019 Kidins220 ablation in astrocytes causes defects in Ca2+ signaling linked to altered store-operated Ca2+ entry and strong overexpression of the TRPV4 channel. Kidins220-/- astrocytes are more sensitive to genotoxic stress. Kidins220 expression in astrocytes is required for proper connectivity of co-cultured wild-type neurons. Ca2+ imaging in primary astrocyte cultures (Kidins220 knockout), TRPV4 immunoblotting and immunofluorescence, genotoxic stress assays, neuronal co-culture connectivity analysis Cell death and differentiation Medium 31624352
2021 Kidins220 deficiency causes ventriculomegaly via downregulation of the SNX27-retromer complex, which leads to lysosomal degradation of AQP4 (aquaporin-4). AQP4 was identified as a novel cargo of the SNX27-retromer. Kidins220 deficient mice show loss of AQP4 at ventricular ependyma and in astrocytes. SNX27 silencing decreases AQP4 levels; SNX27 overexpression restores AQP4 in Kidins220-deficient astrocytes, establishing the KIDINS220-SNX27-retromer-AQP4 pathway. Kidins220 knockout mouse phenotyping, AQP4 immunofluorescence, SNX27-retromer interaction assays, lysosome inhibition experiments, SNX27 knockdown and overexpression in astrocytes, iNPH patient brain tissue immunostaining Molecular psychiatry High 34002021
2021 A novel homozygous in-frame deletion mutation in KIDINS220 adjacent to the fourth transmembrane domain diminishes binding of KIDINS220 to TrkA, as demonstrated by co-immunoprecipitation. This reduced TrkA interaction is associated with fetal brain ventriculomegaly and limb contractures, implicating TrkA as a likely mediator of the KIDINS220 loss-of-function phenotype. Co-immunoprecipitation of mutant vs wild-type KIDINS220 with TrkA, fetal brain autopsy/imaging, exome sequencing Human molecular genetics Medium 33205811
2022 XPR1 (phosphate exporter) requires KIDINS220 as a novel partner protein for proper cellular localization and activity. Disruption of the XPR1-KIDINS220 complex by genetic or pharmacologic inhibition of XPR1 in SLC34A2-high cancer cell lines results in toxic intracellular phosphate accumulation and formation of acidic vacuolar structures preceding cell death. CRISPR-Cas9 loss-of-function screens, cellular localization assays, phosphate efflux assays, vacuolar morphology imaging, XPR1 genetic/pharmacologic inhibition in cancer cell lines and in vivo xenograft models Nature cancer High 35437317
2004 Kidins220 is expressed in immature dendritic cells (DC), where it localizes at the leading edge membrane protrusion in a lipid raft compartment. F-actin co-localizes with Kidins220 at the leading edge and is required for its polarized membrane localization. Disruption of lipid rafts with methyl-β-cyclodextrin causes loss of Kidins220 polarization, cell rounding, and inhibition of DC motility. Immunocytochemistry, confocal microscopy, methyl-β-cyclodextrin raft disruption, F-actin depolymerization, motility assays in monocyte-derived and peripheral blood DC European journal of immunology Medium 14971036

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 The Piwi-piRNA pathway provides an adaptive defense in the transposon arms race. Science (New York, N.Y.) 808 17975059
1979 Arms races between and within species. Proceedings of the Royal Society of London. Series B, Biological sciences 781 42057
2010 A nucleator arms race: cellular control of actin assembly. Nature reviews. Molecular cell biology 745 20237478
2008 Cohesins functionally associate with CTCF on mammalian chromosome arms. Cell 720 18237772
2000 Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annual review of biochemistry 465 10966480
2012 Rules of engagement: molecular insights from host-virus arms races. Annual review of genetics 421 23145935
2011 Synthetic chromosome arms function in yeast and generate phenotypic diversity by design. Nature 343 21918511
2015 The butterfly plant arms-race escalated by gene and genome duplications. Proceedings of the National Academy of Sciences of the United States of America 341 26100883
1992 Development, multiplexing, and application of ARMS tests for common mutations in the CFTR gene. American journal of human genetics 215 1379414
2001 Amplification-refractory mutation system (ARMS) analysis of point mutations. Current protocols in human genetics 207 18428319
2023 Antibiotics and Bacterial Resistance-A Short Story of an Endless Arms Race. International journal of molecular sciences 174 36982857
1998 Dynein arms are oscillating force generators. Nature 149 9641685
2010 The arms race between tomato and Fusarium oxysporum. Molecular plant pathology 147 20447279
2000 Identification and cloning of Kidins220, a novel neuronal substrate of protein kinase D. The Journal of biological chemistry 141 10998417
2010 A comparison of ARMS and DNA sequencing for mutation analysis in clinical biopsy samples. Journal of experimental & clinical cancer research : CR 135 20925915
2001 Serine proteinase inhibitors from nematodes and the arms race between host and pathogen. Trends in biochemical sciences 117 11246026
2014 The molecular arms race between African trypanosomes and humans. Nature reviews. Microbiology 95 24975321
2014 Deception and manipulation: the arms of leishmania, a successful parasite. Frontiers in immunology 84 25368612
2022 Evolutionary Landscapes of Host-Virus Arms Races. Annual review of immunology 80 35080919
2004 Mdmx and Mdm2: brothers in arms? Cell cycle (Georgetown, Tex.) 72 15254433
2013 Protective arms of the renin-angiotensin-system in neurological disease. Clinical and experimental pharmacology & physiology 69 23735163
2012 Kidins220/ARMS as a functional mediator of multiple receptor signalling pathways. Journal of cell science 66 22562556
2011 Kidins220/ARMS mediates the integration of the neurotrophin and VEGF pathways in the vascular and nervous systems. Cell death and differentiation 64 22048155
2016 Cladosporium fulvum Effectors: Weapons in the Arms Race with Tomato. Annual review of phytopathology 62 27215970
2009 Gemfibrozil, stretching arms beyond lipid lowering. Immunopharmacology and immunotoxicology 60 19694602
2006 A quantitative assay for JAK2(V617F) mutation in myeloproliferative disorders by ARMS-PCR and capillary electrophoresis. Leukemia 60 16572198
2022 Phosphate dysregulation via the XPR1-KIDINS220 protein complex is a therapeutic vulnerability in ovarian cancer. Nature cancer 59 35437317
2005 Sister chromatid cohesion along arms and at centromeres. Trends in genetics : TIG 58 15946764
2007 A call to arms: coevolution of animal viruses and host innate immune responses. Trends in genetics : TIG 57 17467114
2009 Kidins220/ARMS downregulation by excitotoxic activation of NMDARs reveals its involvement in neuronal survival and death pathways. Journal of cell science 56 19759287
2009 Kidins220/ARMS modulates the activity of microtubule-regulating proteins and controls neuronal polarity and development. The Journal of biological chemistry 54 19903810
2006 Kidins220/ARMS is transported by a kinesin-1-based mechanism likely to be involved in neuronal differentiation. Molecular biology of the cell 54 17079733
2004 Lipid raft disruption triggers protein kinase C and Src-dependent protein kinase D activation and Kidins220 phosphorylation in neuronal cells. The Journal of biological chemistry 53 15096499
2010 Kidins220/ARMS regulates Rac1-dependent neurite outgrowth by direct interaction with the RhoGEF Trio. Journal of cell science 52 20519585
2020 PRMT6-mediated H3R2me2a guides Aurora B to chromosome arms for proper chromosome segregation. Nature communications 51 32001712
2022 Alternative functions of CRISPR-Cas systems in the evolutionary arms race. Nature reviews. Microbiology 50 34992260
2019 The interaction of phages and bacteria: the co-evolutionary arms race. Critical reviews in biotechnology 50 31793351
2017 Geminiviruses and Plant Hosts: A Closer Examination of the Molecular Arms Race. Viruses 50 28914771
2006 The extended arms of DNA-binding domains: a tale of tails. Trends in biochemical sciences 50 16920361
2017 Tuned SMC Arms Drive Chromosomal Loading of Prokaryotic Condensin. Molecular cell 49 28238653
2016 Tooth agenesis and orofacial clefting: genetic brothers in arms? Human genetics 48 27699475
2009 Ankyrin Repeat-rich Membrane Spanning/Kidins220 protein regulates dendritic branching and spine stability in vivo. Developmental neurobiology 48 19449316
2011 Kidins220/ARMS is an essential modulator of cardiovascular and nervous system development. Cell death & disease 46 22048169
2016 Heterozygous KIDINS220/ARMS nonsense variants cause spastic paraplegia, intellectual disability, nystagmus, and obesity. Human molecular genetics 45 27005418
2005 DNA arms do the legwork to ensure the directionality of lambda site-specific recombination. Current opinion in structural biology 44 16368232
2015 A co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome. Parasitology 43 25656360
2013 Bearing arms against osteoarthritis and sarcopenia: when cartilage and skeletal muscle find common interest in talking together. Drug discovery today 41 23973339
2020 Sequence analysis in Bos taurus reveals pervasiveness of X-Y arms races in mammalian lineages. Genome research 37 33208454
1997 Frequent gains on chromosome arms 1q and/or 8q in human endometrial cancer. Human genetics 36 9341884
2023 Unveil the Secret of the Bacteria and Phage Arms Race. International journal of molecular sciences 34 36901793
2018 Y-box proteins combine versatile cold shock domains and arginine-rich motifs (ARMs) for pleiotropic functions in RNA biology. The Biochemical journal 33 30206185
2012 Kidins220 accumulates with tau in human Alzheimer's disease and related models: modulation of its calpain-processing by GSK3β/PP1 imbalance. Human molecular genetics 33 23118350
2010 The ARMS/Kidins220 scaffold protein modulates synaptic transmission. Molecular and cellular neurosciences 33 20547223
2023 The p-Arms of Human Acrocentric Chromosomes Play by a Different Set of Rules. Annual review of genomics and human genetics 31 36854315
2011 A selective role for ARMS/Kidins220 scaffold protein in spatial memory and trophic support of entorhinal and frontal cortical neurons. Experimental neurology 31 21419124
2008 Targeting Plk1 to chromosome arms and regulating chromosome compaction by the PICH ATPase. Cell cycle (Georgetown, Tex.) 31 18418076
2007 PKD1, PKD2, and their substrate Kidins220 regulate neurotensin secretion in the BON human endocrine cell line. The Journal of biological chemistry 31 18048355
2017 Homozygous KIDINS220 loss-of-function variants in fetuses with cerebral ventriculomegaly and limb contractures. Human molecular genetics 30 28934391
2016 Stepping Out of the Shade: Control of Neuronal Activity by the Scaffold Protein Kidins220/ARMS. Frontiers in cellular neuroscience 30 27013979
2016 MiR-4638-5p inhibits castration resistance of prostate cancer through repressing Kidins220 expression and PI3K/AKT pathway activity. Oncotarget 30 27329728
2015 Condensin Relocalization from Centromeres to Chromosome Arms Promotes Top2 Recruitment during Anaphase. Cell reports 30 26686624
2018 Centromeres License the Mitotic Condensation of Yeast Chromosome Arms. Cell 29 30318142
2013 Kidins220/ARMS associates with B-Raf and the TCR, promoting sustained Erk signaling in T cells. Journal of immunology (Baltimore, Md. : 1950) 29 23359496
2003 Juxtacentromeric region of human chromosome 21: a boundary between centromeric heterochromatin and euchromatic chromosome arms. Gene 27 12909339
2020 The IRE1 and PERK arms of the unfolded protein response promote survival of rhabdomyosarcoma cells. Cancer letters 26 32679165
2011 Analysis of mitochondrial DNA point mutation heteroplasmy by ARMS quantitative PCR. Current protocols in human genetics 26 21234877
2019 Trans-kingdom RNA interactions drive the evolutionary arms race between hosts and pathogens. Current opinion in genetics & development 25 31472442
2016 Arms Race between Enveloped Viruses and the Host ERAD Machinery. Viruses 25 27657106
2023 Friends in Arms: Flavonoids and the Auxin/Cytokinin Balance in Terrestrialization. Plants (Basel, Switzerland) 24 36771601
2021 Kidins220 deficiency causes ventriculomegaly via SNX27-retromer-dependent AQP4 degradation. Molecular psychiatry 24 34002021
2019 BRAF mutation analysis by ARMS-PCR refines thyroid nodule management. Clinical endocrinology 24 31441082
2015 Development of a neuroprotective peptide that preserves survival pathways by preventing Kidins220/ARMS calpain processing induced by excitotoxicity. Cell death & disease 24 26492372
2020 Host-Virus Arms Races Drive Elevated Adaptive Evolution in Viral Receptors. Journal of virology 23 32493827
2018 Regulation of BDNF Release by ARMS/Kidins220 through Modulation of Synaptotagmin-IV Levels. The Journal of neuroscience : the official journal of the Society for Neuroscience 23 29769266
2012 Quantification of mtDNA mutation heteroplasmy (ARMS qPCR). Methods in molecular biology (Clifton, N.J.) 23 22215557
2012 Ankyrin repeat-rich membrane spanning protein (kidins220) is required for neurotrophin and ephrin receptor-dependent dendrite development. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 22699907
2023 Plant-virus arms race beyond RNA interference. Trends in plant science 21 37953079
2014 ARMS for EGFR mutation analysis of cytologic and corresponding lung adenocarcinoma histologic specimens. Journal of cancer research and clinical oncology 21 25156817
2007 Developmental and activity-dependent regulation of ARMS/Kidins220 in cultured rat hippocampal neurons. Developmental neurobiology 21 17587220
2004 The neuronal protein Kidins220 localizes in a raft compartment at the leading edge of motile immature dendritic cells. European journal of immunology 21 14971036
2021 Arms race between rice and viruses: a review of viral and host factors. Current opinion in virology 20 33530035
2016 Activation of PKR by short stem-loop RNAs containing single-stranded arms. RNA (New York, N.Y.) 20 27208315
2025 Transposon-host arms race: a saga of genome evolution. Trends in genetics : TIG 19 39979178
2022 LAPped in Proof: LC3-Associated Phagocytosis and the Arms Race Against Bacterial Pathogens. Frontiers in cellular and infection microbiology 19 35047422
2012 Rotavirus-host cell interactions: an arms race. Current opinion in virology 19 22658208
2021 Gradual opening of Smc arms in prokaryotic condensin. Cell reports 18 33910021
2020 Host protein chaperones, RNA helicases and the ubiquitin network highlight the arms race for resources between tombusviruses and their hosts. Advances in virus research 18 32711728
2023 The arms race between bacteria CBASS and bacteriophages. Frontiers in immunology 17 37575224
2023 Conserved and divergent arms of the antiviral response in the duplicated genomes of salmonid fishes. Genomics 16 37286012
2019 Kidins220/ARMS controls astrocyte calcium signaling and neuron-astrocyte communication. Cell death and differentiation 16 31624352
2015 Kidins220/ARMS binds to the B cell antigen receptor and regulates B cell development and activation. The Journal of experimental medicine 16 26324445
2023 Morin post-treatment surpassed calpeptin in ameliorating 3-NP-induced cortical neurotoxicity via modulation of glutamate/calpain axis, Kidins220, and BDNF/TrkB/AKT/CREB trajectory. International immunopharmacology 15 36736222
2021 TrkA mediates effect of novel KIDINS220 mutation in human brain ventriculomegaly. Human molecular genetics 15 33205811
2020 Brothers in Arms: Structure, Assembly and Function of Arenaviridae Nucleoprotein. Viruses 15 32708976
2019 Calreticulin arms NK cells against leukemia. Oncoimmunology 15 32002282
2015 Greasy tactics in the plant-pathogen molecular arms race. Journal of experimental botany 15 25725095
2010 The ankyrin repeat-rich membrane spanning (ARMS)/Kidins220 scaffold protein is regulated by activity-dependent calpain proteolysis and modulates synaptic plasticity. The Journal of biological chemistry 15 20943655
2023 A billion years arms-race between viruses, virophages, and eukaryotes. eLife 14 37358563
2015 Functional Interaction between the Scaffold Protein Kidins220/ARMS and Neuronal Voltage-Gated Na+ Channels. The Journal of biological chemistry 14 26037926
2012 Kidins220/ARMS is a novel modulator of short-term synaptic plasticity in hippocampal GABAergic neurons. PloS one 14 22563401

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