Affinage

DPYSL3

Dihydropyrimidinase-related protein 3 · UniProt Q14195

Length
570 aa
Mass
62.0 kDa
Annotated
2026-06-09
60 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DPYSL3 (CRMP4/Ulip) is a neuronal phosphoprotein and cytoskeletal regulator that controls axonal growth, growth cone dynamics, and cell migration by integrating extracellular guidance and inhibitory signals with actin and microtubule organization (PMID:8551352, PMID:17301178). As a downstream effector of myelin-associated inhibitors, CRMP4 physically and functionally complexes with RhoA at actin-rich growth cone regions to transduce axon outgrowth inhibition, and disrupting the CRMP4b-RhoA interaction relieves this inhibition on myelin and chondroitin sulfate proteoglycan substrates (PMID:17301178, PMID:22583768, PMID:26995506). This activity is gated by phosphorylation: GSK3β acts within a MAI-GSK3β-CRMP4-RhoA signaling axis, and Cdk5 and DYRK2 phosphorylate CRMP4 to govern neuronal positioning during development (PMID:20410116, PMID:22898304). CRMP4 transduces Semaphorin-3E signaling through its association with the Sema3E receptor complex and MAP6, requiring detergent-resistant-membrane domain integrity and acting through Akt/GSK3, with Crmp4-loss producing aberrant fornix development (PMID:34860155). Beyond guidance, CRMP4 localizes to spindle microtubules and is required for chromosomal alignment and mitotic progression in a GSK3-dependent manner (PMID:21179545). It is also a calpain substrate, cleaved upon NMDA excitotoxic and oxidative stress in a NOS/L-VGCC-dependent manner, generating fragments that drive Wallerian degeneration and death signaling (PMID:16135096, PMID:16987501, PMID:34190355); in ALS models CRMP4 binds the retrograde motor dynein to mislocalize from distal axons to the soma and promote motor neuron loss, which is reversed by blocking the CRMP4-dynein interaction (PMID:34190355). In non-neuronal contexts CRMP4 regulates invasive migration: it interacts with Ezrin to stabilize a focal adhesion complex, drives MRTF/SRF-dependent actin polymerization, and its expression is controlled by promoter CpG methylation, while it negatively regulates osteoblast differentiation via BMP2 and RhoA/FAK signaling (PMID:24339867, PMID:41715156, PMID:25888628, PMID:28019696). Its activity is further modulated by SUMOylation at K374, which weakens its interaction with the Cav1.2 L-type Ca2+ channel (PMID:34645092).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1996 Medium

    Established CRMP4 as a neuronal phosphoprotein positioned at sites of axon growth, framing it as a candidate effector of growth and guidance signals.

    Evidence cDNA cloning with immunolocalization to neurites, growth cones, and NMJ plus NGF-stimulated phosphorylation in neuronal cells

    PMID:8551352

    Open questions at the time
    • No molecular partners or downstream effectors identified
    • Functional consequence of phosphorylation undefined
  2. 1998 Medium

    Showed CRMP4 exists as multiple phosphorylated isoforms developmentally and during NGF-induced differentiation, reinforcing phosphoregulation as a control point.

    Evidence 2D immunoblot of in vitro translated protein, RT-PCR, PC12 differentiation assay

    PMID:9652388

    Open questions at the time
    • Kinases responsible not identified
    • Isoform-specific functions unresolved
  3. 2006 High

    Defined CRMP4 as a stress-regulated calpain substrate, linking excitotoxic and oxidative insults to its proteolytic processing.

    Evidence In vitro purified calpain digestion, calpain inhibitor and NOS/L-VGCC pharmacology in primary cortical neurons, immunoblotting (PMIDs 16135096, 16987501)

    PMID:16135096 PMID:16987501

    Open questions at the time
    • Function of the cleavage fragments not determined here
    • Cleavage site not mapped
  4. 2010 High

    Identified the CRMP4b-RhoA complex as the effector arm that transduces myelin/CSPG inhibition into growth cone collapse, and placed GSK3β phosphorylation upstream of complex formation.

    Evidence Reciprocal Co-IP, siRNA knockdown, competitive peptide inhibitor and neurite outgrowth assays on inhibitory substrates, plus GSK3β manipulation (PMIDs 17301178, 20410116)

    PMID:17301178 PMID:20410116

    Open questions at the time
    • Structural basis of CRMP4-RhoA binding not resolved
    • How phosphorylation gates the interaction at the residue level unclear
  5. 2010 Medium

    Extended CRMP4 function beyond neurons by showing it localizes to the mitotic spindle and is a GSK3 substrate required for chromosomal alignment.

    Evidence Immunofluorescence to spindle microtubules, siRNA knockdown, phosphomimetic/phospho-dead mutants, chromosomal alignment assays

    PMID:21179545

    Open questions at the time
    • Spindle-binding partners not identified
    • Single-lab observation in cultured cells
  6. 2012 Medium

    Genetic and developmental work established CRMP4 as a phosphorylation-dependent determinant of neuronal positioning and MAG-mediated axon inhibition/protection.

    Evidence Crmp4-/- DRG neurons with MAG and Vincristine assays; zebrafish morpholino knockdown with Cdk5/DYRK2 phosphomimetic rescue (PMIDs 22583768, 22898304)

    PMID:22583768 PMID:22898304

    Open questions at the time
    • Direct kinase-substrate phosphosites not all mapped
    • Mechanism linking phosphorylation to cytoskeletal output incomplete
  7. 2013 Medium

    Opened a cancer/cell-migration axis by showing CRMP4 binds Ezrin to stabilize a focal adhesion complex and that a disease-associated variant has gain-of-toxic-function in motor neurons.

    Evidence Co-IP and MRM proteomics with adhesion/migration assays in pancreatic cancer cells; in vitro expression of an rs147541241 missense variant in motor neurons (PMIDs 24339867, 23568759)

    PMID:23568759 PMID:24339867

    Open questions at the time
    • Ezrin interaction interface not mapped
    • Variant pathogenicity tested only in a single cell assay
  8. 2014 High

    Provided atomic-resolution structures of human CRMP4, defining its fold and oligomerization residues and a structural framework for disease mutations.

    Evidence X-ray crystallography of truncated and full-length human CRMP-4

    PMID:24914979

    Open questions at the time
    • No co-structures with partners (RhoA, dynein, Ezrin)
    • Structure does not capture phosphorylated or fragment states
  9. 2015 Medium

    Established epigenetic control of CRMP4 expression and its role as a metastasis suppressor acting through Akt/Rac1 and MMP-9.

    Evidence TALE-based locus-specific CpG methylation/demethylation with in vitro and in vivo invasion assays and pathway analysis in prostate cancer cells

    PMID:25888628

    Open questions at the time
    • Mechanism connecting CRMP4 to Akt/Rac1 not defined
    • Direct vs indirect regulation of MMP-9 unresolved
  10. 2018 Medium

    Defined a feedback loop in which calpain-2-generated CRMP4 fragments and EMT regulators reciprocally control migration, with CRMP4 suppressing SNAIL/TWIST and PAK2-dependent motility while opposing mitotic defects.

    Evidence Calpain-2 cleavage, nuclear fractionation, ChIP for DNMT1 at the CRMP4 promoter, and siRNA knockdown with EMT/vimentin and PAK2 readouts in cancer cells (PMIDs 29601651, 30498031)

    PMID:29601651 PMID:30498031

    Open questions at the time
    • In vivo relevance of nuclear CRMP4 fragment limited
    • Direct targets of the N-terminal fragment incompletely mapped
  11. 2017 Medium

    Demonstrated a skeletal role: CRMP4 negatively regulates osteoblast differentiation through BMP2 and RhoA/FAK signaling.

    Evidence Crmp4-/- mice with bone histomorphometry plus gain/loss-of-function osteoblast assays and pathway analysis

    PMID:28019696

    Open questions at the time
    • Direct molecular link between CRMP4 and BMP2 receptor signaling unclear
    • Single-lab in vivo finding
  12. 2021 High

    Resolved a death-signaling mechanism in ALS: CRMP4 binds dynein for retrograde transport that mislocalizes it to the soma and drives motor neuron loss.

    Evidence Co-IP for CRMP4-dynein, localization in ALS patient tissue and SOD1G93A mice, and competitive inhibition rescue in C9orf72 iPSC-MNs and ALS mice

    PMID:34190355

    Open questions at the time
    • Dynein adaptor/cargo selection mechanism undefined
    • How somatic CRMP4 accumulation triggers death not fully mechanistic
  13. 2021 High

    Placed CRMP4 in the Semaphorin-3E pathway via the Sema3E receptor complex and MAP6, requiring DRM and cytoskeleton-binding domains to signal through Akt/GSK3 for fornix development.

    Evidence Co-IPs (CRMP4-MAP6, CRMP4-Sema3E receptor), Crmp4-/- fornix anatomy, DRM fractionation, and domain-deletion functional analysis

    PMID:34860155

    Open questions at the time
    • Stoichiometry within the receptor complex unknown
    • How DRM localization mechanistically enables signaling unresolved
  14. 2021 Medium

    Showed CRMP4 activity is tuned by SUMOylation at K374, which modulates its Cav1.2 interaction, neurite outgrowth, and pain sensitivity.

    Evidence GST-pulldown with SUMO1/2/3, Co-IP, electrophysiology, and in vivo paw withdrawal behavioral assay

    PMID:34645092

    Open questions at the time
    • SUMO E3 ligase and deSUMOylase not identified
    • Link between Cav1.2 coupling and pain behavior indirect
  15. 2022 Medium

    Defined CRMP4's roles in adult hippocampal neurogenesis and, with CRMP1/CRMP2, in cortical and hippocampal neuronal migration and mossy fiber pruning, clarifying paralog redundancy and specificity.

    Evidence Crmp4-/- and CRMP1/2/4 multi-mutant mice with birthdating, marker immunostaining, in utero electroporation, and Nrp2 epistasis (PMIDs 35122931, 34297816, 34932871)

    PMID:34297816 PMID:34932871 PMID:35122931

    Open questions at the time
    • Molecular distinction between paralog functions incomplete
    • Cell-intrinsic vs niche contributions not separated
  16. 2024 Medium

    Revealed a cell-autonomous glial role: microglial CRMP4 promotes proliferation and shapes neuroinflammatory responses.

    Evidence Microglia-specific conditional Crmp4 KO with LPS substantia nigra injection, Iba1 immunostaining, and Arg1/IL-10 analysis

    PMID:38914219

    Open questions at the time
    • Signaling mechanism in microglia undefined
    • Single model and stimulus tested
  17. 2026 Medium

    Connected CRMP4 to a transcriptional-cytoskeletal output by showing it drives actin polymerization and MRTF/SRF activation to promote invasive migration in endometriosis.

    Evidence CRMP4 KO/overexpression, free-actin quantification, MRTF nuclear translocation, SRF reporter, migration assays, and in vivo lesion model

    PMID:41715156

    Open questions at the time
    • Direct mechanism linking CRMP4 to actin nucleation unclear
    • Whether MRTF/SRF axis operates in other CRMP4 contexts untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CRMP4's phosphorylation, SUMOylation, and calpain-cleavage states are integrated to switch it between growth-promoting, growth-inhibiting, and pro-death functions across cell types remains unresolved.
  • No unified model linking PTM state to partner choice (RhoA vs dynein vs Ezrin vs MRTF)
  • Structures of CRMP4 in modified or complexed states lacking
  • Tissue-specific regulators of CRMP4 modification largely unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2 GO:0005634 nucleus 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1640170 Cell Cycle 1
Partners
CACNA1CDYNC1H1EZRINMAP6NF1RHOASEMA3E

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 DPYSL3/Ulip is a neuronal 64-85 kDa phosphoprotein localized in neurites, growth cones, and at the neuromuscular junction; its phosphorylation is regulated in response to nerve growth factor, indicating a functional role in neuritic outgrowth and axonal guidance. cDNA cloning, immunolocalization in neurites/growth cones/NMJ, NGF-stimulated phosphorylation assay The Journal of neuroscience Medium 8551352
1998 DPYSL3/Ulip4 exists in multiple differentially phosphorylated isoforms as shown by 2D immunoblot of in vitro translated protein, and its mRNA expression is regulated during development and NGF-induced differentiation of PC12 cells. 2D immunoblot of in vitro translated protein, RT-PCR, PC12 NGF differentiation assay European journal of biochemistry Medium 9652388
2005 DPYSL3 is a calpain substrate: NMDA excitotoxicity and H2O2 oxidative stress cause calpain-mediated cleavage of DPYSL3 (62 kDa → 60 kDa doublet) in primary cortical neurons; calpain inhibitors block this cleavage, and purified calpain digestion in vitro recapitulates the cleavage product. In vitro calpain digestion, calpain inhibitor treatment in primary cortical neurons, immunoblotting Journal of neurochemistry High 16135096
2006 NMDA-induced calpain-mediated DPYSL3 truncation requires NOS activation and ROS-dependent activation of L-type voltage-gated Ca2+ channels (L-VGCC): NOS inhibitor L-NAME and L-VGCC blocker nimodipine prevented NMDA-induced DPYSL3 truncation and cell death, while NO donor SNP triggered the same calpain-mediated truncation. Pharmacological inhibition (L-NAME, nimodipine, MK801), NO donor treatment, Ca2+ imaging, immunoblotting in primary cortical neurons Brain research Medium 16987501
2007 CRMP4b physically and functionally interacts with RhoA; siRNA knockdown of CRMP4 promotes neurite outgrowth on myelin substrates, and disruption of CRMP4b-RhoA binding with a competitive inhibitor attenuates neurite outgrowth inhibition on myelin and aggrecan. Nogo stimulation causes colocalization of CRMP4b and RhoA at growth cone actin-rich regions. Co-immunoprecipitation, siRNA knockdown, competitive peptide inhibitor, neurite outgrowth assays on inhibitory substrates, immunofluorescence colocalization The Journal of neuroscience High 17301178
2008 Neurofibromin interacts with CRMP-4 (and CRMP-2) in rat brain; CDK5 is required for the interaction between neurofibromin and CRMP-2, suggesting CDK5 phosphorylation regulates these interactions. Immunoprecipitation, mass spectrometry, immunoprecipitation-immunoblot, CDK5 inhibition Biochemical and biophysical research communications Medium 18313395
2010 GSK3β is inactivated by myelin-associated inhibitors (MAIs) and, as a consequence, regulates phosphorylation of CRMP4 and its ability to complex with RhoA; overexpression of GSK3β attenuates myelin inhibition, and a CRMP4 antagonist attenuates the inhibitory effects of GSK3β inhibitors. This establishes GSK3β-CRMP4-RhoA as a signaling axis downstream of MAIs. Overexpression/inhibition of GSK3β, CRMP4 antagonist peptide, neurite outgrowth assay, phosphorylation analysis The Journal of neuroscience High 20410116
2010 CRMP4 localizes to spindle microtubules during mitosis; loss of CRMP4 disrupts chromosomal alignment and mitotic progression in a GSK3-dependent phosphorylation-dependent manner, identifying CRMP4 as a physiological GSK3 substrate for mitotic progression. Immunofluorescence localization to spindle microtubules, siRNA knockdown, phosphomimetic/phospho-dead mutants, chromosomal alignment assays PloS one Medium 21179545
2012 CRMP4 mediates MAG-induced inhibition of axonal outgrowth and growth cone collapse; loss of CRMP4 (Crmp4-/- DRG neurons) prevents MAG-induced inhibition and increases sensitivity to Vincristine-induced axonal degeneration; MAG-mediated axon protection against Vincristine is suppressed in CRMP4-/- neurons. Crmp4-/- mouse model, DRG neuron culture, MAG treatment, Vincristine-induced degeneration assay, axon outgrowth and growth cone collapse measurement Neuroscience letters Medium 22583768
2012 Phosphorylation of Dpysl3 (CRMP4) by Cdk5 and DYRK2 is required for proper positioning of Rohon-Beard neurons and neural crest cells during neurulation in zebrafish; phosphorylation mimics rescued the ectopic cell positioning phenotype in dpysl2/dpysl3 and cdk5/dyrk2 double morphants. Morpholino knockdown in zebrafish, phosphomimetic rescue constructs, cell transplantation analysis Developmental biology Medium 22898304
2013 DPYSL3 interacts with Ezrin in pancreatic cancer cells; this interaction promotes stabilization of a focal adhesion complex (Ezrin/c-Src/FAK/Talin1) and activating phosphorylation of Ezrin and c-Src, regulating cell adhesion and migration. Co-immunoprecipitation, quantitative proteomics (MRM), functional adhesion/migration assays, phosphorylation analysis PloS one Medium 24339867
2013 A missense variant (rs147541241:A>G) in DPYSL3/CRMP4 expressed in motor neurons reduced axonal growth and accelerated cell death compared to wild-type protein in vitro, suggesting the mutation has a gain-of-toxic-function effect on axonal growth. In vitro expression of mutant DPYSL3 in motor neuron cell culture, axon growth measurement, cell survival assay Human mutation Medium 23568759
2014 Crystal structures of human CRMP-4 (truncated and full-length) were determined, revealing that CRMP-4 adopts a fold similar to other CRMPs and identifying residues important for homo- and hetero-oligomerization; structures also provided insight into functionally relevant mutations of the DPYSL3 gene. X-ray crystallography (crystal structure determination with lattice-translocation disorder correction) Acta crystallographica. Section D, Biological crystallography High 24914979
2015 Locus-specific CpG demethylation of the CRMP4 promoter in metastatic PC3 prostate cancer cells abolished metastasis, whereas locus-specific methylation in non-metastatic 22Rv1 cells induced metastasis; CRMP4-mediated metastasis suppression required activation of Akt/Rac1 signaling and down-regulation of MMP-9. TALE-DNA methyltransferase/demethylase-mediated locus-specific CpG modification, in vitro/in vivo migration/invasion assays, signaling pathway analysis Oncotarget Medium 25888628
2015 CRMP4 deletion (Crmp4-/-) in mice leads to neuroprotection after spinal cord injury and reductions in inflammatory response and scar formation; CRMP4 expression is observed in inflammatory cells as well as neurons after injury, and injury increases inhibitory/toxic phosphorylated forms of CRMP4. Crmp4-/- mouse model, spinal cord transection, locomotor behavior assessment, immunohistochemistry for inflammatory markers and scar formation Scientific reports Medium 25652774
2016 Crmp4 deletion overrides CSPG-induced inhibition of axon growth in DRG neurons in vitro; CRMP4 levels are increased in DRGs after spinal cord injury in vivo; Crmp4-/- mice exhibit axonal growth of sensory neurons and recovery of nociceptive function after spinal transection. Crmp4-/- mouse, DRG neuron culture on CSPG substrate, axon growth measurement, in vivo spinal cord injury model, nociceptive behavioral testing Molecular and cellular neurosciences Medium 26995506
2017 CRMP4 negatively regulates osteoblast differentiation via inhibition of BMP2 signaling and RhoA/FAK signaling; Crmp4-/- mice display increased bone mass, mineral apposition rate, and bone formation rate; Crmp4-/- osteoblasts exhibit enhanced BMP2 signaling, increased RhoA/FAK activation, and altered cell spreading and proliferation through p27Kip1/cyclin D1. Crmp4-/- mouse model, in vitro gain/loss-of-function in stromal cells, osteoblast differentiation assays, BMP2 signaling analysis, RhoA/FAK pathway analysis, bone histomorphometry Journal of bone and mineral research Medium 28019696
2018 DPYSL3 knockdown in claudin-low breast cancer cells reduced proliferation, enhanced motility, increased EMT marker expression, caused multinucleated cell accumulation (mitotic defect) associated with vimentin microfilament collapse and increased vimentin phosphorylation; DPYSL3 suppressed EMT regulators SNAIL and TWIST and opposed PAK2-dependent migration; in turn, EMT regulators induce DPYSL3 expression (negative feedback). siRNA knockdown, cell proliferation and motility assays, immunoblot for EMT markers, microscopy for multinucleated cells and vimentin network, PAK2 inhibitor studies Proceedings of the National Academy of Sciences of the United States of America Medium 30498031
2018 Calpain-2 cleaves CRMP4 into an N-terminal fragment that promotes migration and invasion in prostate cancer cells via nuclear translocation and E2F1-mediated DNMT1 expression; NF-κB RelA/p65 (with Ser276 phosphorylation) recruits DNMT1 to methylate the CRMP4 promoter, suppressing CRMP4 transcription; CRMP4 suppresses metastasis via inhibiting VEGFC through Semaphorin3B-Neuropilin2 signaling. In vitro calpain-2 cleavage assay, nuclear fractionation, siRNA/overexpression, ChIP for DNMT1 at CRMP4 promoter, VEGFC pathway analysis, cell migration/invasion assays The Prostate Medium 29601651
2020 CRMP4 facilitates both Wallerian degeneration in distal axon segments (via calpain-dependent formation of harmful CRMP4 fragments) and regeneration of proximal axon segments following sciatic nerve injury; Crmp4-/- mice show impaired sensory axon regeneration and Wallerian degeneration after sciatic nerve injury. Crmp4-/- mouse model (male and female), sciatic nerve injury, in vitro DRG neuron axotomy assays, calpain fragment detection by immunoblot eNeuro Medium 32001550
2021 CRMP4 levels are increased in ALS motor neuron cell bodies but decreased in distal axons; this subcellular mislocalization is caused by increased interaction of CRMP4 with the retrograde motor protein dynein, mediating CRMP4 transport from distal axons to soma and promoting motor neuron loss; blocking the CRMP4-dynein interaction reduces motor neuron loss in C9orf72-mutant human iPSC-derived MNs and SOD1G93A ALS mice. Immunofluorescence in human ALS tissue and SOD1G93A mice, Co-immunoprecipitation for CRMP4-dynein, competitive inhibitor of CRMP4-dynein interaction, iPSC-derived motor neuron survival assay The EMBO journal High 34190355
2021 CRMP4 interacts with the Semaphorin-3E tripartite receptor complex and with MAP6; CRMP4-KO mice display abnormal fornix development resembling Sema3E-KO mice; DRM domain integrity is required to transduce Sema3E signaling through Akt/GSK3; the cytoskeleton-binding domain of CRMP4 is required for Sema3E growth-promoting activity. Co-immunoprecipitation (CRMP4-MAP6, CRMP4-Sema3E receptor complex), Crmp4-/- mouse fornix anatomy, DRM fractionation, domain deletion mutants, Akt/GSK3 pathway analysis eLife High 34860155
2021 CRMP4 (but not CRMP1) is involved in infrapyramidal bundle (IPB) pruning of mossy fibers in the hippocampus; genetic interaction analysis indicates CRMP2 and CRMP4 have distinct functions, with CRMP2 mediating IPB pruning via Nrp2 (semaphorin/neuropilin pathway); altered synaptic terminals of mossy fibers were observed in CRMP2 and CRMP4 mutant mice. CRMP4-/- mouse, CRMP2/CRMP4 double mutants, IPB anatomy, genetic interaction analysis with Nrp2 mutants Developmental neurobiology Medium 34932871
2021 CRMP4 is SUMOylated at K374 by SUMO1, SUMO2, and SUMO3; SUMO2 interacts with CRMP4 but not with K374 mutant; CRMP4 deSUMOylation promotes neurite outgrowth and strengthens its interaction with Cav1.2 L-type Ca2+ channel; CRMP4 promotes calcium influx via Cav1.2, and overexpression increases thermal pain sensitivity in rats, an effect strengthened by deSUMOylation. GST-pulldown with SUMO1/2/3, Co-IP, immunofluorescence colocalization, neurite outgrowth assay, whole-cell patch clamp, in vivo paw withdrawal latency Journal of integrative neuroscience Medium 34645092
2022 CRMP4 is required for positioning and maturation of newly generated neurons in adult hippocampal neurogenesis; in Crmp4-/- mice, DCX-positive cells are ectopically located in the granule cell layer and the ratio of calretinin-positive new neurons is increased while EdU/NeuN double-positive mature neurons are decreased, indicating CRMP4 regulates migration and maturation of adult-born neurons. Crmp4-/- mouse model, BrdU/EdU birthdating, immunostaining for DCX/calretinin/NeuN, confocal microscopy Neuroscience letters Medium 35122931
2022 CRMP2 phosphorylation by Cdk5 and redundant functions of CRMP1 and CRMP4 are required for proper neuronal migration in developing cerebral cortex and hippocampus; triple mutant (CRMP1 KO; CRMP2 KI/KI; CRMP4 KO) mice show disturbed laminar positioning of cortical neurons and ectopic neurons in hippocampal regions. Triple mutant mouse model (KO/KI combinations), BrdU birthdating, in utero electroporation, cortical layer and hippocampal anatomy analysis Cerebral cortex Medium 34297816
2024 Microglia-specific CRMP4 deletion reduces microglial proliferation after LPS injection into substantia nigra and suppresses arginase-1 expression; CRMP4 is involved in LPS-induced neuroinflammation and suppresses microglial proliferation in a cell-autonomous manner. Microglia-specific Crmp4 conditional KO mouse, LPS injection model, Iba1 immunostaining, IL-10 and Arg1 expression analysis Brain research Medium 38914219
2026 CRMP4 promotes actin polymerization in ectopic endometrial stromal cells and facilitates nuclear translocation of MRTF, activating SRF and downstream target genes related to migration and invasion; CRMP4 silencing inhibits endometriosis lesion growth in vivo. siRNA/lentiviral CRMP4 KO and overexpression, free-actin quantification, immunofluorescence/MRTF nuclear translocation, SRF reporter, Transwell/wound-healing assays, in vivo mouse model Journal of translational medicine Medium 41715156

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Expression patterns of immature neuronal markers PSA-NCAM, CRMP-4 and NeuroD in the hippocampus of young adult and aged rodents. Journal of neuroscience research 164 12391592
1996 Identification and molecular characterization of Unc-33-like phosphoprotein (Ulip), a putative mammalian homolog of the axonal guidance-associated unc-33 gene product. The Journal of neuroscience : the official journal of the Society for Neuroscience 127 8551352
1998 The Ulip family phosphoproteins--common and specific properties. European journal of biochemistry 102 9652388
2007 Identification of CRMP4 as a convergent regulator of axon outgrowth inhibition. The Journal of neuroscience : the official journal of the Society for Neuroscience 90 17301178
2010 GSK3 beta regulates myelin-dependent axon outgrowth inhibition through CRMP4. The Journal of neuroscience : the official journal of the Society for Neuroscience 89 20410116
2000 Differential expression of collapsin response mediator proteins (CRMP/ULIP) in subsets of oligodendrocytes in the postnatal rodent brain. Molecular and cellular neurosciences 65 11085871
1999 Ulip/CRMP proteins are recognized by autoantibodies in paraneoplastic neurological syndromes. The European journal of neuroscience 62 10594648
2005 Calpain-mediated truncation of dihydropyrimidinase-like 3 protein (DPYSL3) in response to NMDA and H2O2 toxicity. Journal of neurochemistry 47 16135096
2018 DPYSL3 modulates mitosis, migration, and epithelial-to-mesenchymal transition in claudin-low breast cancer. Proceedings of the National Academy of Sciences of the United States of America 42 30498031
2015 Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase. Oncotarget 38 25888628
2012 Dpysl2 (CRMP2) and Dpysl3 (CRMP4) phosphorylation by Cdk5 and DYRK2 is required for proper positioning of Rohon-Beard neurons and neural crest cells during neurulation in zebrafish. Developmental biology 36 22898304
2013 Quantitative proteomic profiling identifies DPYSL3 as pancreatic ductal adenocarcinoma-associated molecule that regulates cell adhesion and migration by stabilization of focal adhesion complex. PloS one 32 24339867
2015 Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation. Scientific reports 30 25652774
2013 A rare motor neuron deleterious missense mutation in the DPYSL3 (CRMP4) gene is associated with ALS. Human mutation 29 23568759
2006 Involvement of nitric oxide synthase and ROS-mediated activation of L-type voltage-gated Ca2+ channels in NMDA-induced DPYSL3 degradation. Brain research 29 16987501
2008 Neurofibromin interacts with CRMP-2 and CRMP-4 in rat brain. Biochemical and biophysical research communications 25 18313395
2016 VEGF promotes gastric cancer development by upregulating CRMP4. Oncotarget 22 26934554
1998 Post-meiotic expression of the mouse dihydropyrimidinase-related protein 3 (DRP-3) gene during spermiogenesis. Molecular reproduction and development 21 9712324
2014 Crystal structure of human CRMP-4: correction of intensities for lattice-translocation disorder. Acta crystallographica. Section D, Biological crystallography 20 24914979
2010 GSK3 regulates mitotic chromosomal alignment through CRMP4. PloS one 20 21179545
2018 Inhibition of cell-adhesion protein DPYSL3 promotes metastasis of lung cancer. Respiratory research 19 29514686
2017 microRNA-130a is an oncomir suppressing the expression of CRMP4 in gastric cancer. OncoTargets and therapy 19 28831264
2017 Human CRMP4 mutation and disrupted Crmp4 expression in mice are associated with ASD characteristics and sexual dimorphism. Scientific reports 18 29196732
2012 CRMP4 mediates MAG-induced inhibition of axonal outgrowth and protection against Vincristine-induced axonal degeneration. Neuroscience letters 18 22583768
2018 Calpain-2 triggers prostate cancer metastasis via enhancing CRMP4 promoter methylation through NF-κB/DNMT1 signaling pathway. The Prostate 15 29601651
2016 Deletion of Crmp4 attenuates CSPG-induced inhibition of axonal growth and induces nociceptive recovery after spinal cord injury. Molecular and cellular neurosciences 15 26995506
2020 Intra-Amniotic Delivery of CRMP4 siRNA Improves Mesenchymal Stem Cell Therapy in a Rat Spina Bifida Model. Molecular therapy. Nucleic acids 14 32330869
2017 CRMP4 Inhibits Bone Formation by Negatively Regulating BMP and RhoA Signaling. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 14 28019696
2017 Suppression of Prostate Cancer Metastasis by DPYSL3-Targeted saRNA. Advances in experimental medicine and biology 14 28639202
2010 Injury-induced CRMP4 expression in adult sensory neurons; a possible target gene for ciliary neurotrophic factor. Neuroscience letters 14 20800647
2007 Effect of binocular retinal lesions on CRMP2 and CRMP4 but not Dyn I and Syt I expression in adult cat area 17. The European journal of neuroscience 14 17425566
2017 Prospective Study of CRMP4 Promoter Methylation in Prostate Biopsies as a Predictor For Lymph Node Metastases. Journal of the National Cancer Institute 13 28122909
2003 Induction of CRMP-4 in striatum of adult rat after transient brain ischemia. Acta pharmacologica Sinica 13 14653945
2016 CRMP1 and CRMP4 are required for proper orientation of dendrites of cerebral pyramidal neurons in the developing mouse brain. Brain research 12 27836492
2022 Allopregnanolone suppresses glioblastoma survival through decreasing DPYSL3 and S100A11 expression. The Journal of steroid biochemistry and molecular biology 11 35114375
2021 A CRMP4-dependent retrograde axon-to-soma death signal in amyotrophic lateral sclerosis. The EMBO journal 11 34190355
2020 Collapsin Response Mediator Protein 4 (CRMP4) Facilitates Wallerian Degeneration and Axon Regeneration following Sciatic Nerve Injury. eNeuro 11 32001550
2014 Upregulation of CRMP4, a new prostate cancer metastasis suppressor gene, inhibits tumor growth in a nude mouse intratibial injection model. International journal of oncology 9 25338524
2007 Expression and regulation of Xenopus CRMP-4 in the developing nervous system. The International journal of developmental biology 9 17554687
2019 Crmp4-KO Mice as an Animal Model for Investigating Certain Phenotypes of Autism Spectrum Disorders. International journal of molecular sciences 8 31137494
2018 CRMP2 and CRMP4 Are Differentially Required for Axon Guidance and Growth in Zebrafish Retinal Neurons. Neural plasticity 8 30034463
2016 Targeting CRMP-4 by lentivirus-mediated RNA interference inhibits SW480 cell proliferation and colorectal cancer growth. Experimental and therapeutic medicine 8 27698685
2002 CRMP-4 expression in the adult cerebral cortex and other telencephalic areas of the lizard Podarcis hispanica. Brain research. Developmental brain research 8 12480143
2022 Requirement of CRMP2 Phosphorylation in Neuronal Migration of Developing Mouse Cerebral Cortex and Hippocampus and Redundant Roles of CRMP1 and CRMP4. Cerebral cortex (New York, N.Y. : 1991) 6 34297816
2020 Phosphorylation of CRMP2 is required for migration and positioning of Purkinje cells: Redundant roles of CRMP1 and CRMP4. Brain research 6 32156571
2018 Combined analysis of CRMP4 methylation levels and CAPRA-S score predicts metastasis and outcomes in prostate cancer patients. Asian journal of andrology 6 28382925
2008 Collapsin response mediator protein-4 (CRMP-4) expression in posthaching development of song control nuclei in Bengalese finches. Brain research bulletin 6 18598844
2021 The impact of CRMP4 SUMOylation on the Cav1.2 interaction, neurite outgrowth and thermal pain sensitivity. Journal of integrative neuroscience 5 34645092
2021 CRMP4-mediated fornix development involves Semaphorin-3E signaling pathway. eLife 5 34860155
2015 Up-regulation of DRP-3 long isoform during the induction of neural progenitor cells by glutamate treatment in the ex vivo rat retina. Biochemical and biophysical research communications 5 26071357
2020 Low Incidence of High-Grade Pancreatic Intraepithelial Neoplasia Lesions in a Crmp4 Gene-Deficient Mouse Model of Pancreatic Cancer. Translational oncology 4 32105991
2022 CRMP4 Up-regulates M2 Macrophages and Myeloid-derived Suppressor Cells to Promote Pancreatic Cancer in Mice. Anticancer research 3 35093877
2021 Regulation of axon pruning of mossy fiber projection in hippocampus by CRMP2 and CRMP4. Developmental neurobiology 3 34932871
2022 CRMP4 is required for the positioning and maturation of newly generated neurons in adult mouse hippocampus. Neuroscience letters 2 35122931
2022 Early Detection of Male-Predominant Phenotypes in the Pattern of Ultrasonic Vocalizations Emitted by Autism Spectrum Disorder Model (Crmp4-Knockout) Mice. Brain sciences 2 35625052
2022 CRMP2 and CRMP4 are required for the formation of commissural tracts in the developing zebrafish forebrain. Developmental neurobiology 2 35929227
2015 Development of a cell permeable competitive antagonist of RhoA and CRMP4 binding, TAT-C4RIP, to promote neurite outgrowth. Journal of molecular neuroscience : MN 2 25015230
2024 The role of CRMP4 in LPS-induced neuroinflammation. Brain research 1 38914219
2026 Research on the mechanism of CRMP4-mediated cytoskeletal actin polymerization in promoting invasive migration of stromal cells in endometriosis. Journal of translational medicine 0 41715156
2023 microRNA-130a is an Oncomir Suppressing the Expression of CRMP4 in Gastric Cancer [Retraction]. OncoTargets and therapy 0 37694104

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