ArticleProceedings of the National Academy of Sciences of the United States of America2016
Hierarchical CRMP2 posttranslational modifications control NaV1.7 function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 131 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
- Organelle regulation of SUMOylation: regulatory mechanisms and therapeutic application.Journal of advanced research · 2026Review
- Anti-CV2/CRMP5 autoantibodies as drivers of sensory neuron excitability and pain in rats.Nature communications · 2025Article
- Sensory neuron-expressed FGF13 controls nociceptive signaling in diabetic neuropathy models.The Journal of clinical investigation · 2025Article
- Sculpting excitable membranes: voltage-gated ion channel delivery and distribution.Nature reviews. Neuroscience · 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
- SUMO Regulation of Ion Channels in Health and Disease.Physiology (Bethesda, Md.) · 2025Review
- Sodium channels as a new target for pain treatment.Frontiers in pharmacology · 2025Review
- Article
- Effects of DeSUMOylated Spastin on AMPA Receptor Surface Delivery and Synaptic Function Are Enhanced by Phosphorylating at Ser210.Molecular neurobiology · 2024Article
- A Novel Ubiquitin Ligase Adaptor PTPRN Suppresses Seizure Susceptibility through Endocytosis of NaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- 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
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- Regulating neuronal excitability: The role ofPNAS nexus · 2024Article
- A peptidomimetic modulator of the CaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- The CaScience signaling · 2023Article
- Identification and targeting of a unique NaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Contribution of the dihydropyrimidinase-like proteins family in synaptic physiology and in neurodevelopmental disorders.Frontiers in neuroscience · 2023Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Voltage-gated sodium channels are crucial determinants of neuronal excitability and signaling. Trafficking of the voltage-gated sodium channel NaV1.7 is dysregulated in neuropathic pain. We identify a trafficking program for NaV1.7 driven by hierarchical interactions with posttranslationally modified versions of the binding partner collapsin response mediator protein 2 (CRMP2). The binding described between CRMP2 and NaV1.7 was enhanced by conjugation of CRMP2 with small ubiquitin-like modifier (SUMO) and further controlled by the phosphorylation status of CRMP2. We determined that CRMP2 SUMOylation is enhanced by prior phosphorylation by cyclin-dependent kinase 5 and antagonized by Fyn phosphorylation. As a consequence of CRMP2 loss of SUMOylation and binding to NaV1.7, the channel displays decreased membrane localization and current density, and reduces neuronal excitability. Preventing CRMP2 SUMOylation with a SUMO-impaired CRMP2-K374A mutant triggered NaV1.7 internalization in a clathrin-dependent manner involving the E3 ubiquitin ligase Nedd4-2 (neural precursor cell expressed developmentally down-regulated protein 4) and endocytosis adaptor proteins Numb and epidermal growth factor receptor pathway substrate 15. Collectively, our work shows that diverse modifications of CRMP2 cross-talk to control NaV1.7 activity and illustrate a general principle for regulation of NaV1.7.
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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.