Affinage

DPYSL2

Dihydropyrimidinase-related protein 2 · UniProt Q16555

Length
572 aa
Mass
62.3 kDa
Annotated
2026-06-09
100 papers in source corpus 44 papers cited in narrative 43 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DPYSL2 (CRMP2) is a multifunctional cytosolic phosphoprotein that governs neuronal polarity, axon and dendrite growth, and ion channel surface trafficking (PMID:11477421, PMID:22279220). It promotes axon specification by binding tubulin heterodimers with higher affinity than assembled microtubules and driving microtubule assembly through its C-terminal helix H19, an activity required for axon induction, elongation and branching (PMID:12134159, PMID:28878401). CRMP2 couples this cytoskeletal function to transport by linking soluble tubulin to anterograde Kinesin-1 via direct binding to KLC1, and by regulating Numb-mediated endocytosis of the adhesion molecule L1 at growth cones (PMID:15935053, PMID:12942088). Its activity is gated by a layered post-translational program: Cdk5 phosphorylation at Ser522 primes sequential GSK-3β phosphorylation at Thr514/Thr509, and Rho-kinase phosphorylation at Thr555, each reducing tubulin/Numb binding and inactivating CRMP2 downstream of guidance cues such as Sema3A and ephrin-A5 (PMID:15676027, PMID:15652488, PMID:16260611); oxidation-driven Cys504 disulfide dimerization amplified by thioredoxin further licenses GSK-3 phosphorylation, while FER-mediated tyrosine phosphorylation at Y479/Y499 blocks tetramerization and microtubule bundling (PMID:21521879, PMID:29396402). At presynaptic and sensory terminals CRMP2 binds CaV2.2 to enhance its surface expression and neurotransmitter/neuropeptide release in a Cdk5-Ser522-dependent manner, and a hierarchical modification cascade in which Cdk5-primed SUMOylation at Lys374 by Ubc9 maintains NaV1.7 at the membrane, whereas loss of SUMOylation recruits a Numb/Nedd4-2/Eps15 complex to drive clathrin-mediated NaV1.7 internalization — an axis that is a dominant, sex-influenced determinant of chronic neuropathic pain (PMID:19755421, PMID:27940916, PMID:33478555, PMID:32569093). CRMP2 is required in vivo for dendritic patterning, synaptic plasticity and stereotyped axon pruning, and its expression is transcriptionally repressed by BMP-SMAD and TGF-β-SMAD/TGIF signaling during cortical neuronal migration and morphogenesis (PMID:22279220, PMID:27249678, PMID:31919978, PMID:20926379, PMID:29695415).

Mechanistic history

Synthesis pass · year-by-year structured walk · 39 steps
  1. 2001 High

    Established CRMP2 as a determinant of neuronal polarity, answering whether a single cytosolic factor could specify axon identity.

    Evidence Overexpression and dominant-negative truncation in cultured hippocampal neurons with morphological readout

    PMID:11477421

    Open questions at the time
    • Did not define the molecular activity driving axon formation
    • No endogenous loss-of-function in vivo
  2. 2002 High

    Identified tubulin-heterodimer binding and microtubule assembly promotion as the molecular basis of CRMP2's growth-promoting activity.

    Evidence In vitro tubulin-binding and polymerization assays plus dominant-negative mutant expression in neurons

    PMID:12134159

    Open questions at the time
    • Structural interface with tubulin not yet resolved
    • Did not address how transport is coordinated with assembly
  3. 2003 High

    Connected CRMP2 to membrane traffic by showing it regulates Numb-mediated endocytosis of L1 at growth cones.

    Evidence Co-IP, siRNA knockdown, dominant-negative expression and L1 endocytosis assays in hippocampal neurons

    PMID:12942088

    Open questions at the time
    • Mechanism linking endocytosis to axon growth not fully defined
    • Generality beyond L1 cargo unknown at the time
  4. 2000 High

    Mapped a multi-site phosphorylation signature (Thr509/Ser518/Ser522) on CRMP2 in Alzheimer neurofibrillary tangles, raising the question of which kinases impose it and its functional consequence.

    Evidence Immunoaffinity purification, site-directed mutagenesis and in vitro kinase assay on AD brain

    PMID:10757975

    Open questions at the time
    • Did not identify the responsible kinases
    • Causal role in disease not established
  5. 2005 High

    Defined the kinase logic inactivating CRMP2: Cdk5 priming at Ser522 enables sequential GSK-3β phosphorylation (Thr509/Thr514) and Rho-kinase phosphorylation (Thr555), each disrupting tubulin/Numb binding downstream of Sema3A and ephrin-A5.

    Evidence In vitro kinase assays, phospho-specific antibodies, phospho-mutants, cdk5-/- lysates and growth cone collapse assays

    PMID:15652488 PMID:15676027 PMID:16260611

    Open questions at the time
    • Phosphatases reversing these marks not yet defined
    • How distinct guidance cues select specific sites unclear
  6. 2005 High

    Showed CRMP2 bridges soluble tubulin to anterograde Kinesin-1 via direct KLC1 binding, mechanistically coupling cargo binding to axonal transport.

    Evidence Direct binding/pulldown assays, Co-IP, FRAP of GFP-tubulin and siRNA knockdown

    PMID:15935053

    Open questions at the time
    • Regulation of complex assembly by phosphorylation not tested here
    • Relationship to retrograde transport unresolved
  7. 2008 High

    Identified PP1-family phosphatase as the eraser of GSK3-targeted CRMP2 sites and explained why the Cdk5 site resists dephosphorylation, rationalizing AD-associated hyperphosphorylation.

    Evidence In vitro phosphatase assays, pharmacological inhibitors and Pin1 transgenic mice

    PMID:18460467

    Open questions at the time
    • Precise phosphatase isoform not pinned down
    • In vivo disease causality not addressed
  8. 2008 Medium

    Placed CRMP2 in a neurofibromin complex in a CDK5-dependent manner, hinting at a tumor-suppressor link to CRMP2 regulation.

    Evidence Co-IP from rat brain lysate with roscovitine inhibition and mass spectrometry

    PMID:18313395

    Open questions at the time
    • Functional consequence of the interaction not defined in this study
    • Single lab Co-IP
  9. 2009 High

    Established CRMP2 as a direct regulator of CaV2.2 N-type calcium channel surface expression and neurotransmitter/neuropeptide release in central and sensory neurons.

    Evidence Co-IP, domain mapping, surface biotinylation, patch-clamp and glutamate/CGRP release with knockdown

    PMID:19755421 PMID:19903690

    Open questions at the time
    • Phospho-dependence of CaV2.2 binding not yet defined
    • In vivo physiological/pathological role untested at this point
  10. 2009 Medium

    Showed local mTOR-p70S6K signaling selectively upregulates CRMP2 translation to drive axon specification, adding a translational control layer.

    Evidence Rapamycin treatment, p70S6K expression, 5'UTR reporter assays and rescue in axons

    PMID:19648118

    Open questions at the time
    • Direct demonstration of localized CRMP2 protein synthesis limited
    • Single lab
  11. 2009 Medium

    Proposed CRMP2 antagonizes retrograde transport through direct dynein heavy-chain binding, distinguishing kinesin and dynein interaction regions.

    Evidence Co-IP, domain mapping and dynein-driven microtubule transport assay in COS-7 cells

    PMID:19659462

    Open questions at the time
    • Effect shown in non-neuronal cells only
    • Single lab, no in vivo validation
  12. 2010 Medium

    Extended CRMP2's trafficking role to non-neuronal endosomal transport, linking MICAL-L1/EHD1 recycling vesicles to dynein motors.

    Evidence Co-IP, siRNA knockdown, transferrin recycling assay and dynamitin overexpression

    PMID:20801876

    Open questions at the time
    • Neuronal relevance not directly tested
    • Single lab
  13. 2010 High

    Identified BMP-SMAD1/4 transcriptional repression of CRMP2 as a control point for multipolar-to-bipolar transition during cortical radial migration.

    Evidence ChIP and in utero electroporation with RNAi/dominant-negative constructs in cortical slices

    PMID:20926379

    Open questions at the time
    • Upstream signals tuning BMP-CRMP2 axis in vivo incompletely mapped
  14. 2011 High

    Reconstituted an oxidation-phosphorylation cascade: Sema3A/MICAL-derived H2O2 forms a Cys504 disulfide dimer that engages thioredoxin to stimulate GSK-3 phosphorylation and growth cone collapse.

    Evidence In vitro reconstitution with purified proteins, mass spectrometry, non-reducing SDS-PAGE, Cys504 mutagenesis and collapse assay

    PMID:21521879

    Open questions at the time
    • In vivo contribution of the redox switch to guidance not quantified
    • Sources of physiological oxidant beyond Sema3A unclear
  15. 2011 High

    Translated CRMP2-CaV2.2 biology into therapeutics, showing peptide disruption (TAT-CBD3) reduces transmitter release and reverses neuropathic pain in vivo.

    Evidence TAT-CBD3 peptide, in vivo pain behavior and dorsal horn electrophysiology

    PMID:21642979

    Open questions at the time
    • Peptide selectivity across CRMP2 interactions not fully delineated
  16. 2011 High

    Implicated CRMP2 in NMDAR (GluN2B) surface trafficking and excitotoxic neuroprotection, broadening its receptor-trafficking role.

    Evidence Lentiviral knockdown, TAT-CBD3 peptide, Ca2+ imaging, electrophysiology and a TBI model

    PMID:21832084

    Open questions at the time
    • Direct CRMP2-NMDAR interface not structurally defined here
  17. 2012 High

    Demonstrated in vivo that Cdk5-Ser522 phosphorylation organizes dendritic fields, with CRMP1/CRMP2 acting synergistically.

    Evidence CRMP2-S522A knock-in combined with CRMP1 knockout and cortical neuron morphology analysis

    PMID:22279220

    Open questions at the time
    • Molecular effectors downstream of Ser522 in dendrites not isolated
  18. 2012 High

    Linked NgR1/Rho-kinase-driven Thr555 phosphorylation of CRMP2 to axonal degeneration in demyelinating disease, with phospho-resistant T555A protecting axons.

    Evidence NgR1 knockout mice, AAV-T555A rescue and phospho-immunostaining in EAE/optic nerve

    PMID:22544872

    Open questions at the time
    • Downstream degenerative effectors of phospho-CRMP2 unresolved
  19. 2012 Medium

    Showed Cdk5-Ser522 phosphorylation specifically enhances the CRMP2-CaV2.2 interaction, tying the kinase code to calcium channel regulation.

    Evidence Phospho-null/inactive Cdk5 expression, Ca2+ current measurement and Co-IP

    PMID:23022559

    Open questions at the time
    • Single lab
    • Structural basis of phospho-enhanced binding not defined
  20. 2013 High

    Discovered Ubc9-mediated CRMP2 SUMOylation at Lys374 as a positive regulator of NaV1.7 surface expression, opening the sodium-channel trafficking axis.

    Evidence In vivo SUMOylation assays, SUMO protease overexpression, surface biotinylation and electrophysiology of NaV1.7/CaV2.2

    PMID:23510938 PMID:23836888

    Open questions at the time
    • Hierarchical control of SUMOylation by other PTMs not yet established here
  21. 2013 Medium

    Characterized a reversible Cys504-Cys504 dithiol-disulfide quaternary switch, regulated by glutaredoxin 2c, that toggles axon outgrowth.

    Evidence Non-reducing SDS-PAGE, Cys504 mutagenesis, axon outgrowth assay and Grx2c interaction studies

    PMID:24133216

    Open questions at the time
    • Single lab biochemistry
    • In vivo relevance of the conformational switch untested
  22. 2013 Medium

    Expanded CRMP2's channel/receptor partners to GluK5 kainate receptors, NMDAR, and NCX3, with phospho-state-specific consequences for CaV2.2 and exchanger trafficking.

    Evidence Co-IP, phospho-specific antibodies, surface expression and Ca2+ dysregulation assays

    PMID:24227739 PMID:24474686

    Open questions at the time
    • Single-lab Co-IPs
    • Direct versus indirect interactions not all distinguished
  23. 2015 High

    Optimized CRMP2-CaV2.2 disruption with a membrane-tethered peptide (myr-tat-CBD3), improving potency for analgesia and confirming the trafficking mechanism.

    Evidence Pulldown, colocalization, voltage/current-clamp and inflammatory/postoperative pain models

    PMID:25782368

    Open questions at the time
    • Long-term in vivo specificity and off-target trafficking effects not fully addressed
  24. 2016 High

    Resolved the hierarchical PTM code controlling NaV1.7: Cdk5 phosphorylation promotes Lys374 SUMOylation (antagonized by Fyn), and loss of SUMOylation recruits Nedd4-2/Numb/Eps15 for clathrin-mediated channel internalization.

    Evidence SUMOylation assays, phospho-mutants, surface biotinylation, clathrin inhibition and Co-IP

    PMID:27940916

    Open questions at the time
    • Stoichiometry and dynamics of competing PTMs in vivo not quantified
  25. 2016 High

    Established an in vivo requirement for CRMP2 in synaptic plasticity, NMDAR composition, dendrite development and synapse formation.

    Evidence Brain-specific conditional knockout with LTP electrophysiology, immunostaining and adult neurogenesis knockdown

    PMID:27249678

    Open questions at the time
    • Molecular link between CRMP2 loss and altered NMDAR subunit composition unresolved
  26. 2017 High

    Provided structural rationale for PTM-gated SUMOylation: crystallography shows Lys374 is buried in the tetramer interface but exposed in the monomer, so phospho-induced monomerization licenses SUMOylation.

    Evidence 1.78 Å X-ray structure of mouse CRMP2 with structure-guided mutagenesis

    PMID:28277940

    Open questions at the time
    • Direct structural capture of the SUMOylated/phosphorylated state lacking
  27. 2017 High

    Defined the C-terminal helix H19 as the soluble-tubulin interface distinct from the microtubule-binding tail, mechanistically separating dimer binding from lattice binding.

    Evidence X-ray crystallography, in vitro polymerization, H19 mutagenesis and chick/C. elegans axon assays

    PMID:28878401

    Open questions at the time
    • How phosphorylation reshapes H19-tubulin contacts not structurally shown
  28. 2017 High

    Connected neurofibromin to the CaV2.2 pain axis, showing its loss frees CRMP2 to engage syntaxin 1A and CaV2.2 and increase CGRP release, druggable with t-CNRP1.

    Evidence Co-IP, peptide mapping, CGRP release, surface biotinylation and NF1 pain models

    PMID:28767512

    Open questions at the time
    • Structural interface of the CRMP2-neurofibromin complex undefined
  29. 2018 High

    Identified FER tyrosine phosphorylation at Y479/Y499 as a switch that blocks CRMP2 tetramerization and microtubule bundling, with consequences for taxane sensitivity in cancer.

    Evidence Crystal structure of Y479E phospho-mimetic, in vitro bundling assay, FER inhibition and ovarian cancer xenografts

    PMID:29396402

    Open questions at the time
    • Neuronal relevance of FER-CRMP2 axis not addressed
    • Endogenous FER-CRMP2 dynamics in tumors limited
  30. 2018 High

    Demonstrated Cdk5-CRMP2 phosphorylation at Ser522 is both necessary and sufficient for neuropathic pain, providing bidirectional in vivo causality.

    Evidence siRNA knockdown, intrathecal phospho-null/mimetic mutants and spared nerve injury model

    PMID:31080913

    Open questions at the time
    • Relative contribution of CaV2.2 versus NaV1.7 to the Ser522 pain phenotype not dissected
  31. 2018 High

    Quantified the Ubc9-CRMP2 binding affinity and validated SUMOylation-motif peptide disruption (t-CSM) as an analgesic strategy targeting NaV1.7 trafficking.

    Evidence Microscale thermophoresis, AlphaLISA, cell-penetrating peptide, biotinylation, electrophysiology and SNI model

    PMID:29847471

    Open questions at the time
    • Selectivity of t-CSM for CRMP2 among Ubc9 substrates not fully established
  32. 2018 High

    Identified TGF-β/Smad-TGIF transcriptional repression of CRMP2 as a neurodevelopmental morphogenesis axis disrupted by patient pathway mutations.

    Evidence ChIP, Smad-TGIF Co-IP, in utero electroporation and human iPSC-derived neuron assays

    PMID:29695415

    Open questions at the time
    • Direct CRMP2 mutation causality in patients not established here
  33. 2019 High

    Placed GSK3/CRMP2 as a required, mTOR-independent effector branch for PTEN-knockout-mediated optic nerve regeneration.

    Evidence PTEN conditional KO, GSK3 knock-in mice and AAV-CRMP2-T/A rescue in optic nerve regeneration

    PMID:31453382

    Open questions at the time
    • Downstream cytoskeletal events enabling regeneration not fully mapped
  34. 2019 High

    Defined a NgR1/PlexinA2/CRMP2 ternary complex induced by Nogo-A that restricts corticospinal sprouting and functional recovery after injury.

    Evidence IP-proteomics, cell contraction assay, double-heterozygous mouse genetics and pyramidotomy

    PMID:30804090

    Open questions at the time
    • Direct CRMP2 contact within the ternary complex not structurally resolved
  35. 2019 Medium

    Identified PTP4A3 (PRL-3) as a CRMP2 Thr514 phosphatase in uveal melanoma, linking CRMP2 dephosphorylation/loss to cytoskeletal remodeling and invasion.

    Evidence Phospho-immunoblot, catalytically inactive PTP4A3, CRMP2 knockdown and invasion/xenograft assays

    PMID:30816227

    Open questions at the time
    • Single lab
    • Mechanism connecting CRMP2 loss to stiffness/invasion incompletely defined
  36. 2020 High

    Showed CRMP2 mediates Sema3F as well as Sema3A signaling, controlling stereotyped axon pruning, spine remodeling and ASD-related behavior in vivo.

    Evidence crmp2-/- mice, axon pruning quantification, Sema3F stimulation and behavioral assays

    PMID:31919978

    Open questions at the time
    • Signaling components linking CRMP2 to Sema3F-specific pruning not isolated
  37. 2020 High

    Provided definitive in vivo genetic proof that Lys374 SUMOylation controls peripheral NaV1.7 and neuropathic pain in a sex-specific manner.

    Evidence CRMP2-K374A knock-in mice, surface biotinylation, electrophysiology and sex-stratified pain behavior

    PMID:32569093

    Open questions at the time
    • Molecular basis of the female-specific dependence not resolved
  38. 2021 High

    Defined the endocytic effector complex (Numb/Nedd4-2/Eps15) that internalizes NaV1.7 when CRMP2 is not SUMOylated, completing the bidirectional trafficking switch.

    Evidence siRNA knockdown of endocytic proteins, clathrin inhibition and electrophysiology in CRMP2-K374A knock-in DRG neurons

    PMID:33478555

    Open questions at the time
    • Sequence of recruitment among Numb/Nedd4-2/Eps15 not ordered
    • Sex-difference mechanism still open
  39. 2023 Medium

    Revealed an unexpected RNA-binding function: CRMP2 acts as a synaptic m6A reader of Malat1 lncRNA to support spine formation and fear-extinction memory.

    Evidence m6A RNA-seq, RIP-mass spectrometry, dendritic spine quantification and fear-extinction behavior

    PMID:37669863

    Open questions at the time
    • Structural basis of CRMP2 m6A recognition undefined
    • Limited mechanistic follow-up on the CRMP2 side

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CRMP2's distinct activities — tubulin assembly, motor coupling, ion-channel trafficking, and RNA reading — are spatially and temporally partitioned within a single neuron by its integrated PTM code remains unresolved.
  • No unified structural model integrating phosphorylation, SUMOylation, oxidation and tyrosine modification states
  • Quantitative partitioning of CRMP2 pools among partners in vivo unknown
  • Whether m6A-reading and cytoskeletal roles share the same protein pool untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0003723 RNA binding 1
Localization
GO:0005829 cytosol 3 GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-112316 Neuronal System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5653656 Vesicle-mediated transport 3
Partners
CACNA1BFERKLC1NF1NUMBSCN9ATUBBUBE2I
Complex memberships
CRMP2/KLC1/tubulin transport complexNgR1/PlexinA2/CRMP2 ternary complexNumb/Nedd4-2/Eps15 endocytic complex

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 CRMP-2 is enriched in growing axons of cultured hippocampal neurons; overexpression induces supernumerary axons, and dominant-negative truncation mutants suppress primary axon formation, establishing CRMP-2 as critical for axon induction and neuronal polarity. Overexpression and dominant-negative mutant expression in cultured hippocampal neurons with morphological readout Nature neuroscience High 11477421
2002 CRMP-2 binds tubulin heterodimers with higher affinity than assembled microtubules and promotes microtubule assembly; a deletion mutant lacking the microtubule-assembly region acts dominant-negatively to inhibit axonal growth and branching. In vitro tubulin-binding assays, microtubule polymerization assays, dominant-negative mutant overexpression in neurons Nature cell biology High 12134159
2003 CRMP-2 interacts with Numb; CRMP-2/Numb complex co-localizes with L1 at axonal growth cones, and dominant-negative CRMP-2 or siRNA knockdown inhibits L1 endocytosis and suppresses axon growth, identifying CRMP-2 as a regulator of polarized Numb-mediated endocytosis. Co-immunoprecipitation, siRNA knockdown, dominant-negative expression, L1 endocytosis assay in hippocampal neurons Nature cell biology High 12942088
2005 GSK-3β phosphorylates CRMP-2 at Thr-514 and inactivates it; expression of non-phosphorylatable CRMP-2 or GSK-3β inhibition induces multiple axon-like neurites, while constitutively active GSK-3β impairs neuronal polarization. NT-3 inactivates GSK-3β leading to CRMP-2 dephosphorylation and axon outgrowth. In vitro kinase assay, phospho-specific antibodies, overexpression of constitutively active/kinase-dead mutants, knockdown of CRMP-2 in hippocampal neurons Cell High 15652488
2005 Cdk5 phosphorylates CRMP2 at Ser522; this primes sequential phosphorylation by GSK-3β at Thr509. Dual phosphorylation reduces CRMP2 affinity for tubulin and generates the 3F4 neurofibrillary tangle-associated epitope. Sema3A stimulation enhances this sequential phosphorylation, and CRMP2 Ala-mutants at Ser522 or Thr509 attenuate Sema3A-induced growth cone collapse. In vitro kinase assay, site-directed mutagenesis, phospho-specific antibodies, DRG growth cone collapse assay, cdk5-/- mouse brain lysates Genes to cells High 15676027
2005 Rho kinase phosphorylates CRMP-2 and abolishes its binding to tubulin dimers, microtubules, and Numb, but not to actin. Phosphorylated CRMP-2 localizes exclusively to actin filaments rather than microtubules or clathrin-coated pits in growth cones. Ephrin-A5 induces this phosphorylation via Rho kinase during growth cone collapse. In vitro kinase assay, phospho-mimetic/null mutants, electron microscopy localization, growth cone collapse assay Molecular and cellular biology High 16260611
2005 CRMP-2 C-terminal region directly binds the tetratricopeptide repeat domain of Kinesin light chain 1 (KLC1); soluble tubulin forms a trimeric complex with CRMP-2 and KLC1. Knockdown of KLCs or CRMP-2 impairs anterograde GFP-tubulin transport in axons. Pulldown/direct binding assay, Co-immunoprecipitation, fluorescence recovery after photobleaching (FRAP) of GFP-tubulin, siRNA knockdown Journal of neurochemistry High 15935053
2000 CRMP-2 is highly phosphorylated at Thr-509, Ser-518, and Ser-522 in neurofibrillary tangles of Alzheimer's disease brain; site-directed mutagenesis showed that phosphorylation at all three sites is required for the 3F4 tangle-associated epitope. Immunoaffinity purification, site-directed mutagenesis, in vitro kinase assay with brain extract Biochemistry High 10757975
2009 CRMP-2 directly binds dynein heavy chain at its N-terminus (distinct from the kinesin light chain-binding region); overexpression of dynein-binding CRMP-2 fragments prevents dynein-driven microtubule transport in COS-7 cells, suggesting CRMP-2 interferes with retrograde transport. Co-immunoprecipitation, direct binding domain mapping, dynein-driven microtubule transport assay in COS-7 cells Journal of neurochemistry Medium 19659462
2009 CRMP-2 binds directly to CaV2.2 (N-type Ca2+ channel) at the domain I-II intracellular loop and distal C-terminus; CRMP-2 overexpression increases CaV2.2 surface expression and current density in hippocampal neurons and enhances vesicular glutamate release, while lentiviral knockdown abolishes this effect. Co-immunoprecipitation, cell-surface biotinylation, patch-clamp electrophysiology, glutamate release assay, lentiviral knockdown The Journal of biological chemistry High 19755421
2009 CRMP-2 overexpression in dorsal root ganglion neurons increases CaV2.2 surface levels and current density; siRNA knockdown of CRMP-2 reduces CGRP release by ~54%, establishing CRMP-2 as a regulator of N-type Ca2+ channel activity and transmitter release in sensory neurons. Nucleofection overexpression, siRNA knockdown, patch-clamp electrophysiology, surface biotinylation, CGRP ELISA Journal of cell science High 19903690
2011 Sema3A stimulation generates H2O2 via MICAL, oxidizing CRMP2 to form a disulfide-linked homodimer through Cys-504; oxidized CRMP2 then forms a transient disulfide complex with thioredoxin (TRX), which stimulates GSK-3-mediated phosphorylation of CRMP2, leading to growth cone collapse. This oxidation-phosphorylation cascade was reconstituted in vitro with purified proteins. In vitro reconstitution with purified proteins, mass spectrometry, non-reducing SDS-PAGE, mutagenesis (Cys-504), growth cone collapse assay Science signaling High 21521879
2011 Inhibiting the CRMP-2–CaV2.2 interaction with a TAT-fused CRMP-2-derived peptide (TAT-CBD3) decreases neuropeptide release, excitatory synaptic transmission, and nocifensive/neuropathic pain behaviors in vivo, demonstrating that CRMP-2-mediated enhancement of CaV2.2 function underlies pain hypersensitivity. Peptide inhibitor (TAT-CBD3), in vivo pain behavior assays, electrophysiology in dorsal horn neurons Nature medicine High 21642979
2011 TAT-CBD3 (CRMP-2 peptide) induces NR2B (GluN2B) internalization in dendritic spines, reduces NMDA-evoked Ca2+ influx and currents, and protects neurons from delayed calcium deregulation following glutamate excitotoxicity; CRMP-2 knockdown similarly blocks neuronal death, implicating CRMP-2 in NMDAR surface trafficking. Lentiviral CRMP-2 knockdown, peptide application, Ca2+ imaging, patch-clamp electrophysiology, cortical impact TBI model in vivo The Journal of biological chemistry High 21832084
2012 CRMP-2 phosphorylation at Thr555 (by Rho kinase downstream of NgR1) is increased in degenerating axons in EAE/multiple sclerosis; AAV-mediated expression of phospho-resistant T555A-CRMP-2 limits optic nerve axonal degeneration, establishing NgR1-dependent CRMP-2 phosphorylation as a mechanism of axonal degeneration. NgR1 knockout mice, AAV-T555A-CRMP2 transduction, phospho-specific immunostaining, axonal degeneration quantification Brain High 22544872
2012 Cdk5-mediated phosphorylation of CRMP-2 at Ser522 is required for dendritic field organization in vivo; CRMP2 S522A knock-in mice combined with CRMP1 knockout display severe 'curling' dendritic patterning in cortical neurons, demonstrating synergistic roles of CRMP1 and CRMP2 phosphorylation in dendritic projection. Knock-in mouse generation (CRMP2-S522A), CRMP1 knockout mice, cortical neuron morphology analysis The Journal of neuroscience High 22279220
2012 CRMP-2 phosphorylation by Cdk5 at Ser522 enhances its interaction with CaV2.2; a Cdk5 phospho-null CRMP-2-S522A mutant or inactive Cdk5 abolishes CRMP-2-mediated enhancement of Ca2+ influx via CaV2.2, whereas the Rho kinase site T555A mutant is ineffective. Phospho-null mutant overexpression, inactive Cdk5 co-expression, Ca2+ current measurement, co-immunoprecipitation FEBS letters Medium 23022559
2013 CRMP-2 is SUMOylated by Ubc9 at Lys374 in vivo; removal of the SUMOylation site (K374A or K374A/M375A/D376A mutants) reduces NaV1.7 surface expression and current density, while increasing SUMOylation levels inversely correlates with CaV2.2-mediated calcium influx. In vivo SUMOylation assay, SUMO protease overexpression, surface biotinylation, electrophysiology (NaV1.7 and CaV2.2 currents), calcium imaging The Journal of biological chemistry / Channels High 23510938 23836888
2013 CRMP-2 interacts with the GluK5 subunit of kainate receptors; PKC-mediated phosphorylation of CRMP-2 at T555 (via non-canonical KAR signaling) downregulates membrane CaV2.2, while dephosphorylation at T514 (via GSK3β phosphorylation at S9) promotes neurite outgrowth. Co-immunoprecipitation, phospho-specific antibodies, CaV2.2 surface expression assay, neurite outgrowth assay in DRG neurons The Journal of neuroscience Medium 24227739
2013 CRMP-2 interacts with NMDAR (co-immunoprecipitation) and NCX3 but not NCX1; TAT-CBD3 peptide disrupts CRMP-2–NMDAR interaction without altering NMDAR localization, and simultaneously augments CRMP-2–NCX3 interaction and triggers NCX3 internalization, inhibiting both reverse and forward NCX modes. Co-immunoprecipitation, siRNA knockdown, NCX3 internalization assay, Ca2+ dysregulation assay The Journal of biological chemistry Medium 24474686
2008 Dephosphorylation of CRMP2 at GSK3-targeted residues (Ser-518/Thr-514/Thr-509) is carried out by a protein phosphatase 1 family member in vitro and in neurons; the Cdk5-phosphorylated site (Ser-522) is comparatively resistant to phosphatase treatment, partly due to neighboring basic residues, which may contribute to Alzheimer's disease-associated CRMP2 hyperphosphorylation. In vitro phosphatase assay, pharmacological inhibition (purvalanol, CT99021, IGF-1), Pin1 transgenic mice The Journal of biological chemistry High 18460467
2009 Local mTOR-p70S6K signaling in the axon selectively upregulates translation of CRMP2 and Tau mRNAs via 5'-terminal oligopyrimidine tract elements; rapamycin suppresses axon specification by reducing CRMP2/Tau translation, and exogenous CRMP2 rescues axon formation in rapamycin-treated neurons. Rapamycin treatment, constitutively active p70S6K expression, 5'UTR reporter assays, local translation in axons The Journal of biological chemistry Medium 19648118
2010 CRMP-2 interacts with MICAL-L1 in non-neuronal cells; CRMP-2 depletion causes relocalization of internalized transferrin from peripheral vesicles to the endocytic recycling compartment, an effect blocked by inhibiting dynein (dynamitin overexpression), establishing CRMP-2 as a link between MICAL-L1/EHD1 vesicular transport and dynein motors. Co-immunoprecipitation, siRNA knockdown, transferrin recycling assay, dynamitin overexpression The Journal of biological chemistry Medium 20801876
2010 BMP-SMAD1/4 signaling transcriptionally suppresses CRMP2 expression by binding the CRMP2 promoter (ChIP); CRMP2 knockdown or dominant-negative CRMP2 in utero causes accumulation of multipolar cells and impairs multipolar-to-bipolar transition during radial neuronal migration. ChIP assay, in utero electroporation with RNAi and dominant-negative constructs, cortical slice analysis The Journal of biological chemistry High 20926379
2015 A membrane-tethered myristoylated CRMP-2 peptide (myr-tat-CBD3) more efficiently disrupts CRMP-2–CaV2.2 interaction than the non-myristoylated version, reduces CaV2.2 trafficking, inhibits Ca2+ influx, decreases DRG neuron excitability, and reverses carrageenan-induced thermal hypersensitivity and postoperative pain. Pulldown, confocal immunofluorescence colocalization, voltage-clamp electrophysiology, current-clamp, in vivo pain behavior assays Pain High 25782368
2016 CRMP2 SUMOylation at Lys374 is enhanced by Cdk5-mediated phosphorylation and antagonized by Fyn phosphorylation; SUMOylated CRMP2 binds NaV1.7 to maintain its membrane localization; loss of SUMOylation triggers clathrin-dependent NaV1.7 internalization involving Nedd4-2, Numb, and Eps15. SUMOylation assays, phospho-mutant constructs (Cdk5/Fyn sites), surface biotinylation, clathrin inhibition, Co-immunoprecipitation, CRMP2-K374A mutant expression Proceedings of the National Academy of Sciences High 27940916
2016 Brain-specific Crmp2 knockout mice show reduced hippocampal LTP, abnormal NMDA receptor composition, aberrant dendrite development, and defective synapse formation in CA1 neurons; adult neurogenesis knockdown shows stage-dependent developmental defects, demonstrating CRMP2 is required for synaptic plasticity and neuronal development in vivo. Conditional knockout mice, electrophysiology (LTP), immunostaining, western blot for NMDAR subunits, retroviral knockdown in adult neurogenesis Nature communications High 27249678
2017 X-ray crystal structure (1.78 Å) of mouse CRMP2 reveals Lys374 as the sole biologically relevant SUMOylation site, buried in the tetramer interface but exposed in the monomer; structural basis suggests phosphorylation-induced monomerization exposes Lys374 for SUMOylation. X-ray crystallography (1.78 Å resolution), sequence alignment, structure-function mutagenesis Channels High 28277940
2017 X-ray structural analysis of CRMP2-tubulin interaction shows the C-terminal helix H19 of CRMP2 is the main interface with soluble tubulin dimers (distinct from tail-mediated interaction with assembled microtubules); H19-mediated interaction promotes rapid GTP-state microtubule formation; H19 mutants disturb axon elongation in chick neurons and fail to produce axonal microtubule features in C. elegans. X-ray crystallography, in vitro microtubule polymerization assay, H19 mutagenesis, chick neuron axon elongation assay, C. elegans genetic assay Scientific reports High 28878401
2018 FER tyrosine kinase phosphorylates CRMP2 at Y479 and Y499; crystal structure of CRMP2-Y479E phospho-mimetic reveals this prevents CRMP2 tetramerization, abolishing microtubule bundling activity of the C-terminus. FER depletion increases paclitaxel-induced microtubule stability and cytotoxicity in ovarian cancer cells. X-ray crystallography (CRMP2-Y479E), in vitro microtubule bundling assay, FER kinase inhibition, in vivo xenograft model Nature communications High 29396402
2018 Cdk5-mediated CRMP2 phosphorylation (at Ser522) is increased presynaptically in spinal cord/DRG after spared nerve injury; CRMP2 knockdown reverses mechanical allodynia; intrathecal non-phosphorylatable CRMP2-S522A decreases allodynia while phospho-mimetic S522D induces allodynia in naive rats, establishing Cdk5-CRMP2 phosphorylation as both necessary and sufficient for neuropathic pain. siRNA knockdown, intrathecal expression of phospho-null/mimetic mutants, biochemical fractionation, spared nerve injury model Neurobiology of pain High 31080913
2018 Neurofibromin binds CRMP2 in a CDK5-dependent manner; loss of neurofibromin frees CRMP2 to interact with syntaxin 1A and CaV2.2, increasing CGRP release; a CRMP2-neurofibromin interface-disrupting peptide (t-CNRP1) inhibits Ca2+ influx, reduces CaV2.2 membrane localization, and reverses pain behaviors in NF1-related models. Co-immunoprecipitation, peptide mapping, CGRP release assay, surface biotinylation, in vivo pain behavior Pain High 28767512
2018 The Ubc9–CRMP2 interaction has low micromolar affinity (measured by microscale thermophoresis and AlphaLISA); a CRMP2 SUMOylation motif heptamer peptide (t-CSM) disrupts CRMP2–Ubc9 interaction, reduces CRMP2 SUMOylation, blocks NaV1.7 surface trafficking in sensory neurons, and reverses spinal nerve injury-induced pain. Microscale thermophoresis, AlphaLISA, cell-penetrating peptide, surface biotinylation, electrophysiology, SNI pain model Pain High 29847471
2019 PTEN knockout abrogates GSK3 inhibitory activity on CRMP2; maintaining GSK3 activity (Gsk3 knock-in mice) compromises PTEN-KO-mediated optic nerve regeneration and CRMP2 activity; viral expression of constitutively active CRMP2-T/A rescues regeneration despite reduced mTOR activation, establishing GSK3/CRMP2 as a required pathway for PTEN-KO-mediated axon regeneration. Conditional knockout mice (PTEN), GSK3 knock-in mice, AAV-CRMP2-T/A viral expression, optic nerve regeneration assay Communications biology High 31453382
2019 Nogo-A induces association of NgR1 with CRMP2 in a PlexinA2-dependent manner; NgR1 and PlexinA2 interact genetically to restrict corticospinal axon sprouting after pyramidotomy; double-heterozygous NgR1+/-;PlexinA2+/- mice show greater sprouting and functional recovery, placing CRMP2 in a NgR1/PlexinA2/CRMP2 ternary complex that limits neural repair. Immunoprecipitation proteomics, non-neuronal cell contraction assay, double-heterozygous mouse genetics, pyramidotomy model The Journal of neuroscience High 30804090
2013 Identification of a reversible intermolecular Cys-504–Cys-504 dithiol-disulfide switch in homotetrameric CRMP2 that determines two quaternary conformations controlling axonal outgrowth; this switch is regulated by cytosolic glutaredoxin 2c (Grx2c). Non-reducing SDS-PAGE, site-directed mutagenesis (Cys-504), neuronal axon outgrowth assay, Grx2c interaction studies The Journal of biological chemistry Medium 24133216
2008 Neurofibromin co-immunoprecipitates with CRMP-2 and CRMP-4 (but not CRMP-1) from rat brain; CDK5 activity is required for the neurofibromin–CRMP-2 interaction. Immunoprecipitation from rat brain lysates, CDK5 inhibition (roscovitine), mass spectrometry Biochemical and biophysical research communications Medium 18313395
2020 CRMP2 mediates Sema3F signaling; crmp2-/- mice display prominent defects in stereotyped axon pruning in hippocampus and visual cortex and altered dendritic spine remodeling, consistent with impaired Sema3F (not only Sema3A) signaling; crmp2-/- mice show ASD-related social behavior changes. crmp2-/- knockout mice, axon pruning quantification in hippocampus/visual cortex, Sema3F stimulation in primary neurons, behavioral assays EMBO reports High 31919978
2020 CRMP2 K374A knock-in (CRMP2-SUMOylation-null) mice show reduced NaV1.7 membrane localization and currents specifically in female sensory neurons; these mice fail to develop persistent mechanical allodynia in a neuropathic pain model, demonstrating sex-specific SUMOylation-dependent control of peripheral NaV1.7. CRMP2-K374A knock-in mice, surface biotinylation, electrophysiology, behavioral pain assays, sex-stratified analysis Pain High 32569093
2021 Non-SUMOylated CRMP2 forms a complex with Numb, Nedd4-2, and Eps15 to drive clathrin-mediated endocytosis of NaV1.7; silencing Numb, Nedd4-2, or Eps15 in DRG neurons from CRMP2-K374A female mice restores sodium currents; clathrin inhibition in nerve-injured male CRMP2-K374A mice precipitates allodynia. siRNA knockdown of endocytic proteins, clathrin assembly inhibitor, electrophysiology, CRMP2-K374A knock-in mice Molecular brain High 33478555
2018 TGF-β/Smad canonical signaling suppresses CRMP2 expression through a Smad–TGIF transcriptional repressor complex; this inhibits neurite elongation in mouse and human iPSC-derived neurons; TGF-β pathway mutations found in neurodevelopmental disorder patients disrupt neuronal morphogenesis via this Smad/TGIF/CRMP2 axis. ChIP, co-immunoprecipitation (Smad-TGIF complex), in utero electroporation, human iPSC-derived neuron assays The Journal of neuroscience High 29695415
2023 CRMP2 (DPYSL2) acts as a synaptic m6A reader: it binds m6A-modified Malat1 lncRNA at synapses in the mPFC; disruption of m6A on Malat1 reduces CRMP2 interaction and decreases dendritic spine formation, impairing fear-extinction memory consolidation. m6A RNA-sequencing, RNA immunoprecipitation/mass spectrometry, dendritic spine quantification, fear-extinction behavioral assay The Journal of neuroscience Medium 37669863
2019 PTP4A3 (PRL-3) phosphatase dephosphorylates CRMP2 at T514 in uveal melanoma cells; loss of CRMP2 expression in PTP4A3-expressing cells increases cell migration and invasiveness in vitro/in vivo, accompanied by actin cytoskeleton reorganization and increased cell stiffness; catalytically inactive PTP4A3 does not produce these effects. Phospho-specific immunoblot, PTP4A3 active-site mutant, CRMP2 knockdown, invasion/migration assays, in vivo xenograft Scientific reports Medium 30816227

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity. Cell 777 15652488
2002 CRMP-2 binds to tubulin heterodimers to promote microtubule assembly. Nature cell biology 637 12134159
2001 CRMP-2 induces axons in cultured hippocampal neurons. Nature neuroscience 470 11477421
2005 Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3beta phosphorylation of CRMP2: implication of common phosphorylating mechanism underlying axon guidance and Alzheimer's disease. Genes to cells : devoted to molecular & cellular mechanisms 369 15676027
2005 Phosphorylation by Rho kinase regulates CRMP-2 activity in growth cones. Molecular and cellular biology 232 16260611
2003 CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth. Nature cell biology 218 12942088
2011 Suppression of inflammatory and neuropathic pain by uncoupling CRMP-2 from the presynaptic Ca²⁺ channel complex. Nature medicine 194 21642979
2005 Tubulin and CRMP-2 complex is transported via Kinesin-1. Journal of neurochemistry 180 15935053
2009 An atypical role for collapsin response mediator protein 2 (CRMP-2) in neurotransmitter release via interaction with presynaptic voltage-gated calcium channels. The Journal of biological chemistry 175 19755421
2000 Neurofibrillary tangle-associated collapsin response mediator protein-2 (CRMP-2) is highly phosphorylated on Thr-509, Ser-518, and Ser-522. Biochemistry 167 10757975
2005 Activation of GSK-3 and phosphorylation of CRMP2 in transgenic mice expressing APP intracellular domain. The Journal of cell biology 150 16230462
2004 Role of CRMP-2 in neuronal polarity. Journal of neurobiology 150 14598368
2009 Regulation of N-type voltage-gated calcium channels (Cav2.2) and transmitter release by collapsin response mediator protein-2 (CRMP-2) in sensory neurons. Journal of cell science 126 19903690
2016 Hierarchical CRMP2 posttranslational modifications control NaV1.7 function. Proceedings of the National Academy of Sciences of the United States of America 113 27940916
2016 Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice. Nature communications 109 27249678
2009 Specification of neuronal polarity regulated by local translation of CRMP2 and Tau via the mTOR-p70S6K pathway. The Journal of biological chemistry 108 19648118
2001 Isolation and expression pattern of human Unc-33-like phosphoprotein 6/collapsin response mediator protein 5 (Ulip6/CRMP5): coexistence with Ulip2/CRMP2 in Sema3a- sensitive oligodendrocytes. The Journal of neuroscience : the official journal of the Society for Neuroscience 107 11549731
1999 Expression of the dihydropyrimidinase related protein 2 (DRP-2) in Down syndrome and Alzheimer's disease brain is downregulated at the mRNA and dysregulated at the protein level. Journal of neural transmission. Supplementum 106 10666674
2012 Limiting multiple sclerosis related axonopathy by blocking Nogo receptor and CRMP-2 phosphorylation. Brain : a journal of neurology 99 22544872
2011 Thioredoxin mediates oxidation-dependent phosphorylation of CRMP2 and growth cone collapse. Science signaling 93 21521879
2013 CRMP2 protein SUMOylation modulates NaV1.7 channel trafficking. The Journal of biological chemistry 88 23836888
2012 Phosphorylation of CRMP2 (collapsin response mediator protein 2) is involved in proper dendritic field organization. The Journal of neuroscience : the official journal of the Society for Neuroscience 88 22279220
2011 Neuroprotection against traumatic brain injury by a peptide derived from the collapsin response mediator protein 2 (CRMP2). The Journal of biological chemistry 83 21832084
2007 Proteomic investigation of the ventral rat hippocampus links DRP-2 to escitalopram treatment resistance and SNAP to stress resilience in the chronic mild stress model of depression. Journal of molecular neuroscience : MN 81 17873297
2014 Neuronal deletion of GSK3β increases microtubule speed in the growth cone and enhances axon regeneration via CRMP-2 and independently of MAP1B and CLASP2. BMC biology 73 24923837
2015 A membrane-delimited N-myristoylated CRMP2 peptide aptamer inhibits CaV2.2 trafficking and reverses inflammatory and postoperative pain behaviors. Pain 71 25782368
2012 Cdk5-mediated phosphorylation of CRMP-2 enhances its interaction with CaV2.2. FEBS letters 70 23022559
2014 Collapsin response mediator protein 2 (CRMP2) interacts with N-methyl-D-aspartate (NMDA) receptor and Na+/Ca2+ exchanger and regulates their functional activity. The Journal of biological chemistry 69 24474686
2014 CRMP2: functional roles in neural development and therapeutic potential in neurological diseases. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 67 24402611
2016 Collapsin Response Mediator Protein-2 (CRMP2) is a Plausible Etiological Factor and Potential Therapeutic Target in Alzheimer's Disease: Comparison and Contrast with Microtubule-Associated Protein Tau. Journal of Alzheimer's disease : JAD 62 27079722
2014 Specific binding of lacosamide to collapsin response mediator protein 2 (CRMP2) and direct impairment of its canonical function: implications for the therapeutic potential of lacosamide. Molecular neurobiology 58 24944082
2012 Preconditioning with Ginkgo biloba (EGb 761®) provides neuroprotection through HO1 and CRMP2. Neurobiology of disease 57 22297164
2016 (S)-lacosamide inhibition of CRMP2 phosphorylation reduces postoperative and neuropathic pain behaviors through distinct classes of sensory neurons identified by constellation pharmacology. Pain 55 26967696
2018 Inhibition of the Ubc9 E2 SUMO-conjugating enzyme-CRMP2 interaction decreases NaV1.7 currents and reverses experimental neuropathic pain. Pain 52 29847471
1998 Isolation and characterization of a bovine neural specific protein (CRMP-2) cDNA homologous to unc-33, a C. elegans gene implicated in axonal outgrowth and guidance. Brain research. Molecular brain research 52 9555025
2016 CRMP1 and CRMP2 have synergistic but distinct roles in dendritic development. Genes to cells : devoted to molecular & cellular mechanisms 51 27480924
2015 (S)-Lacosamide Binding to Collapsin Response Mediator Protein 2 (CRMP2) Regulates CaV2.2 Activity by Subverting Its Phosphorylation by Cdk5. Molecular neurobiology 51 25846820
2010 Collapsin response mediator protein-2 (Crmp2) regulates trafficking by linking endocytic regulatory proteins to dynein motors. The Journal of biological chemistry 51 20801876
2009 CRMP-2 directly binds to cytoplasmic dynein and interferes with its activity. Journal of neurochemistry 51 19659462
2017 Dissecting the role of the CRMP2-neurofibromin complex on pain behaviors. Pain 48 28767512
2018 CRMP2 and voltage-gated ion channels: potential roles in neuropathic pain. Neuronal signaling 47 30364788
2016 Inhibition of CRMP2 phosphorylation repairs CNS by regulating neurotrophic and inhibitory responses. Experimental neurology 45 26795088
2010 The suppression of CRMP2 expression by bone morphogenetic protein (BMP)-SMAD gradient signaling controls multiple stages of neuronal development. The Journal of biological chemistry 45 20926379
2009 Increased CRMP2 phosphorylation is observed in Alzheimer's disease; does this tell us anything about disease development? Current Alzheimer research 44 19519308
2018 Canonical TGF-β Signaling Negatively Regulates Neuronal Morphogenesis through TGIF/Smad Complex-Mediated CRMP2 Suppression. The Journal of neuroscience : the official journal of the Society for Neuroscience 43 29695415
2018 Cdk5-mediated CRMP2 phosphorylation is necessary and sufficient for peripheral neuropathic pain. Neurobiology of pain (Cambridge, Mass.) 43 31080913
2015 Differential neuroprotective potential of CRMP2 peptide aptamers conjugated to cationic, hydrophobic, and amphipathic cell penetrating peptides. Frontiers in cellular neuroscience 43 25674050
2013 CRMP2 tethers kainate receptor activity to cytoskeleton dynamics during neuronal maturation. The Journal of neuroscience : the official journal of the Society for Neuroscience 43 24227739
2018 Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation. Nature communications 42 29396402
2017 Structural basis for CRMP2-induced axonal microtubule formation. Scientific reports 42 28878401
2020 CRMP2 mediates Sema3F-dependent axon pruning and dendritic spine remodeling. EMBO reports 41 31919978
2012 Localized role of CRMP1 and CRMP2 in neurite outgrowth and growth cone steering. Developmental neurobiology 41 22378692
2008 Relative resistance of Cdk5-phosphorylated CRMP2 to dephosphorylation. The Journal of biological chemistry 40 18460467
2017 A single structurally conserved SUMOylation site in CRMP2 controls NaV1.7 function. Channels (Austin, Tex.) 39 28277940
2014 Functional variants in DPYSL2 sequence increase risk of schizophrenia and suggest a link to mTOR signaling. G3 (Bethesda, Md.) 39 25416705
2012 A derivative of the CRMP2 binding compound lanthionine ketimine provides neuroprotection in a mouse model of cerebral ischemia. Neurochemistry international 39 23036362
2005 Dihydropyrimidinase-related protein 2 (DRP-2) gene and association to deficit and nondeficit schizophrenia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 39 15858820
2020 Anti-vimentin, anti-TUFM, anti-NAP1L1 and anti-DPYSL2 nanobodies display cytotoxic effect and reduce glioblastoma cell migration. Therapeutic advances in medical oncology 38 32426045
2018 Phosphorylated CRMP2 Regulates Spinal Nociceptive Neurotransmission. Molecular neurobiology 38 30565051
2013 GSK-3α/β-mediated phosphorylation of CRMP-2 regulates activity-dependent dendritic growth. Journal of neurochemistry 37 23470087
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 SUMOylation alters CRMP2 regulation of calcium influx in sensory neurons. Channels (Austin, Tex.) 34 23510938
2020 Studies on CRMP2 SUMOylation-deficient transgenic mice identify sex-specific Nav1.7 regulation in the pathogenesis of chronic neuropathic pain. Pain 32 32569093
2017 Sphingosine-1-Phosphate and the S1P3 Receptor Initiate Neuronal Retraction via RhoA/ROCK Associated with CRMP2 Phosphorylation. Frontiers in molecular neuroscience 32 29066950
2012 Human T lymphotropic virus type 1 increases T lymphocyte migration by recruiting the cytoskeleton organizer CRMP2. Journal of immunology (Baltimore, Md. : 1950) 32 22227566
2019 GSK3-CRMP2 signaling mediates axonal regeneration induced by Pten knockout. Communications biology 31 31453382
2018 Disruption of the psychiatric risk gene Ankyrin 3 enhances microtubule dynamics through GSK3/CRMP2 signaling. Translational psychiatry 31 30046097
2015 Changes in Dpysl2 expression are associated with prenatally stressed rat offspring and susceptibility to schizophrenia in humans. International journal of molecular medicine 31 25847191
2018 CRMP2-Neurofibromin Interface Drives NF1-related Pain. Neuroscience 30 29655575
2013 Challenging the catechism of therapeutics for chronic neuropathic pain: Targeting CaV2.2 interactions with CRMP2 peptides. Neuroscience letters 30 23831344
2020 Downregulation of hippocampal SIRT6 activates AKT/CRMP2 signaling and ameliorates chronic stress-induced depression-like behavior in mice. Acta pharmacologica Sinica 29 32265492
2016 The DPYSL2 gene connects mTOR and schizophrenia. Translational psychiatry 29 27801893
2020 Intravitreal application of AAV-BDNF or mutant AAV-CRMP2 protects retinal ganglion cells and stabilizes axons and myelin after partial optic nerve injury. Experimental neurology 28 31904385
2014 Differential regulation of collapsin response mediator protein 2 (CRMP2) phosphorylation by GSK3ß and CDK5 following traumatic brain injury. Frontiers in cellular neuroscience 28 24904280
2013 Identification of a dithiol-disulfide switch in collapsin response mediator protein 2 (CRMP2) that is toggled in a model of neuronal differentiation. The Journal of biological chemistry 28 24133216
2012 CRMP-2 is involved in axon growth inhibition induced by RGMa in vitro and in vivo. Molecular neurobiology 28 23275173
2022 CRMP2 derived from cancer associated fibroblasts facilitates progression of ovarian cancer via HIF-1α-glycolysis signaling pathway. Cell death & disease 27 35927239
2017 CRMP2 Phosphorylation Drives Glioblastoma Cell Proliferation. Molecular neurobiology 27 28660485
2016 Comprehensive behavioral study and proteomic analyses of CRMP2-deficient mice. Genes to cells : devoted to molecular & cellular mechanisms 27 27582038
2023 Synapse-Enriched m6A-Modified Malat1 Interacts with the Novel m6A Reader, DPYSL2, and Is Required for Fear-Extinction Memory. The Journal of neuroscience : the official journal of the Society for Neuroscience 26 37669863
2018 CRMP2 is necessary for Neurofibromatosis type 1 related pain. Channels (Austin, Tex.) 26 28837387
2008 Neurofibromin interacts with CRMP-2 and CRMP-4 in rat brain. Biochemical and biophysical research communications 25 18313395
2021 Non-SUMOylated CRMP2 decreases NaV1.7 currents via the endocytic proteins Numb, Nedd4-2 and Eps15. Molecular brain 24 33478555
2018 Phosphorylation and SUMOylation of CRMP2 regulate the formation and maturation of dendritic spines. Brain research bulletin 24 29425794
2020 Druggability of CRMP2 for Neurodegenerative Diseases. ACS chemical neuroscience 23 32693579
2019 Both GSK-3β/CRMP2 and CDK5/CRMP2 Pathways Participate in the Protection of Dexmedetomidine Against Propofol-Induced Learning and Memory Impairment in Neonatal Rats. Toxicological sciences : an official journal of the Society of Toxicology 23 31187143
2021 Regulation of CRMP2 by Cdk5 and GSK-3β participates in sevoflurane-induced dendritic development abnormalities and cognitive dysfunction in developing rats. Toxicology letters 22 33548343
2020 Differential Regulation of DNA Methylation at the CRMP2 Promoter Region Between the Hippocampus and Prefrontal Cortex in a CUMS Depression Model. Frontiers in psychiatry 22 32256396
2020 Coordinating Synaptic Signaling with CRMP2. The international journal of biochemistry & cell biology 22 32437854
2019 Plexina2 and CRMP2 Signaling Complex Is Activated by Nogo-A-Liganded Ngr1 to Restrict Corticospinal Axon Sprouting after Trauma. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 30804090
2018 Peroxiredoxin interaction with the cytoskeletal-regulatory protein CRMP2: Investigation of a putative redox relay. Free radical biology & medicine 22 30315937
2013 CNP and DPYSL2 mRNA expression and promoter methylation levels in brain of Alzheimer's disease patients. Journal of Alzheimer's disease : JAD 22 22954668
2024 Small molecule targeting Na V 1.7 via inhibition of CRMP2-Ubc9 interaction reduces pain-related outcomes in a rodent osteoarthritic model. Pain 21 39106443
2019 Genetic inhibition of CRMP2 phosphorylation at serine 522 promotes axonal regeneration after optic nerve injury. Scientific reports 21 31076621
2005 An investigation of the dihydropyrimidinase-like 2 (DPYSL2) gene in schizophrenia: genetic association study and expression analysis. The international journal of neuropsychopharmacology 21 16321170
2020 DPYSL2 is a novel regulator for neural stem cell differentiation in rats: revealed by Panax notoginseng saponin administration. Stem cell research & therapy 19 32299503
2015 Colocalization of phosphorylated forms of WAVE1, CRMP2, and tau in Alzheimer's disease model mice: Involvement of Cdk5 phosphorylation and the effect of ATRA treatment. Journal of neuroscience research 19 26400044
2019 Protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3) promotes the aggressiveness of human uveal melanoma through dephosphorylation of CRMP2. Scientific reports 18 30816227
2018 Chemical shift perturbation mapping of the Ubc9-CRMP2 interface identifies a pocket in CRMP2 amenable for allosteric modulation of Nav1.7 channels. Channels (Austin, Tex.) 18 30081699
2004 Induction of CRMP-2 by GDNF and analysis of the CRMP-2 promoter region. Biochemical and biophysical research communications 18 15207709

Missed literature

Know a paper Affinage missed for DPYSL2? Flag it for the maintainers and the community.

No submissions yet.