ArticleThe Journal of biological chemistry2013
CRMP2 protein SUMOylation modulates NaV1.7 channel trafficking.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 106 citations in OpenAlex.
- Spared but Not Silent: Ion Channel Plasticity in Uninjured Sensory Neurons in Neuropathic Pain.International journal of molecular sciences · 2026Review
- NabioRxiv : the preprint server for biology · 2026Article
- Targeting CRMP2 for Chronic Pain: From Molecular Mechanisms to Therapeutic Strategies.Biomedicines · 2026Review
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Preclinical Animal Models to Investigate the Role of NaLife (Basel, Switzerland) · 2025Review
- SUMOylation and DeSUMOylation: Tug of War of Pain Signaling.Molecular neurobiology · 2025Review
- Article
- Comprehensive Proteomic Profiling of Human Nav1.7-Interacting Proteins Reveals Conserved Regulatory Networks Involved in Nociceptive Signaling.Neuroscience insights · 2025Article
- Peptide and Peptidomimetic Inhibitors Targeting the Interaction of Collapsin Response Mediator Protein 2 with the N-Type Calcium Channel for Pain Relief.ACS pharmacology & translational science · 2024Review
- Regulating neuronal excitability: The role ofPNAS nexus · 2024Article
- Article
- A peptidomimetic modulator of the CaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Identification and targeting of a unique NaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- SUMOtherapeutics for Ischemic Stroke.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Contribution of the dihydropyrimidinase-like proteins family in synaptic physiology and in neurodevelopmental disorders.Frontiers in neuroscience · 2023Review
- Small molecule targeting NaV1.7 via inhibition of the CRMP2-Ubc9 interaction reduces pain in chronic constriction injury (CCI) rats.Channels (Austin, Tex.) · 2022Article
- Changes in peripheral HCN2 channels during persistent inflammation.Channels (Austin, Tex.) · 2021Article
- Selective targeting of NaV1.7 via inhibition of the CRMP2-Ubc9 interaction reduces pain in rodents.Science translational medicine · 2021Article
- The physiological function of different voltage-gated sodium channels in pain.Nature reviews. Neuroscience · 2021Review
- Non-SUMOylated CRMP2 decreases NaMolecular brain · 2021Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Voltage-gated sodium channel (NaV) trafficking is incompletely understood. Post-translational modifications of NaVs and/or auxiliary subunits and protein-protein interactions have been posited as NaV-trafficking mechanisms. Here, we tested if modification of the axonal collapsin response mediator protein 2 (CRMP2) by a small ubiquitin-like modifier (SUMO) could affect NaV trafficking; CRMP2 alters the extent of NaV slow inactivation conferred by the anti-epileptic (R)-lacosamide, implying NaV-CRMP2 functional coupling. Expression of a CRMP2 SUMOylation-incompetent mutant (CRMP2-K374A) in neuronal model catecholamine A differentiated (CAD) cells did not alter lacosamide-induced NaV slow inactivation compared with CAD cells expressing wild type CRMP2. Like wild type CRMP2, CRMP2-K374A expressed robustly in CAD cells. Neurite outgrowth, a canonical CRMP2 function, was moderately reduced by the mutation but was still significantly higher than enhanced GFP-transfected cortical neurons. Notably, huwentoxin-IV-sensitive NaV1.7 currents, which predominate in CAD cells, were significantly reduced in CAD cells expressing CRMP2-K374A. Increasing deSUMOylation with sentrin/SUMO-specific protease SENP1 or SENP2 in wild type CRMP2-expressing CAD cells decreased NaV1.7 currents. Consistent with a reduction in current density, biotinylation revealed a significant reduction in surface NaV1.7 levels in CAD cells expressing CRMP2-K374A; surface NaV1.7 expression was also decreased by SENP1 + SENP2 overexpression. Currents in HEK293 cells stably expressing NaV1.7 were reduced by CRMP2-K374A in a manner dependent on the E2-conjugating enzyme Ubc9. No decrement in current density was observed in HEK293 cells co-expressing CRMP2-K374A and NaV1.1 or NaV1.3. Diminution of sodium currents, largely NaV1.7, was recapitulated in sensory neurons expressing CRMP2-K374A. Our study elucidates a novel regulatory mechanism that utilizes CRMP2 SUMOylation to choreograph NaV1.7 trafficking.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.