ArticleMolecular neurobiology2019
Phosphorylated CRMP2 Regulates Spinal Nociceptive Neurotransmission.
Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Microtubule Cytoskeleton Dysfunction in Chronic Pain: Mechanisms of Transport Failure and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- Targeting CRMP2 for Chronic Pain: From Molecular Mechanisms to Therapeutic Strategies.Biomedicines · 2026Review
- Article
- Unraveling the Nexus: The Role of Collapsin Response Mediator Protein 2 Phosphorylation in Neurodegeneration and Neuroregeneration.Neuromolecular medicine · 2024Review
- 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
- Progress in Core-Shell Magnetic Mesoporous Materials for Enriching Post-Translationally Modified Peptides.Journal of functional biomaterials · 2024Review
- Mid-Infrared Photons Alleviate Tinnitus by Activating the KCNQ2 Channel in the Auditory Cortex.Research (Washington, D.C.) · 2024Article
- Identification and targeting of a unique NaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Neuronal CRMP2 phosphorylation inhibition by the flavonoid, naringenin, contributes to the reversal of spinal sensitization and arthritic pain improvement.Arthritis research & therapy · 2022Article
- Small molecule targeting NaV1.7 via inhibition of the CRMP2-Ubc9 interaction reduces pain in chronic constriction injury (CCI) rats.Channels (Austin, Tex.) · 2022Article
- Selective targeting of NaV1.7 via inhibition of the CRMP2-Ubc9 interaction reduces pain in rodents.Science translational medicine · 2021Article
- AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats.Cell death & disease · 2021Article
- Non-SUMOylated CRMP2 decreases NaMolecular brain · 2021Article
- SARS-CoV-2 spike protein co-opts VEGF-A/neuropilin-1 receptor signaling to induce analgesia.Pain · 2021Article
- Proanthocyanidins Inhibit the Transmission of Spinal Pain Information Through a Presynaptic Mechanism in a Mouse Inflammatory Pain Model.Frontiers in neuroscience · 2021Article
- Inconsistent Time-Dependent Effects of Tetramethylpyrazine on Primary Neurological Disorders and Psychiatric Comorbidities.Frontiers in pharmacology · 2021Article
- Review
- Article
- SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia.bioRxiv : the preprint server for biology · 2020Article
- Differential expression of Cdk5-phosphorylated CRMP2 following a spared nerve injury.Molecular brain · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
The collapsin response mediator protein 2 (CRMP2) has emerged as a central node in assembling nociceptive signaling complexes involving voltage-gated ion channels. Concerted actions of post-translational modifications, phosphorylation and SUMOylation, of CRMP2 contribute to regulation of pathological pain states. In the present study, we demonstrate a novel role for CRMP2 in spinal nociceptive transmission. We found that, of six possible post-translational modifications, three phosphorylation sites on CRMP2 were critical for regulating calcium influx in dorsal root ganglion sensory neurons. Of these, only CRMP2 phosphorylated at serine 522 by cyclin-dependent kinase 5 (Cdk5) contributed to spinal neurotransmission in a bidirectional manner. Accordingly, expression of a non-phosphorylatable CRMP2 (S522A) decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs), whereas expression of a constitutively phosphorylated CRMP2 (S522D) increased the frequency of sEPSCs. The presynaptic nature of CRMP2's actions was further confirmed by pharmacological antagonism of Cdk5-mediated CRMP2 phosphorylation with S-N-benzy-2-acetamido-3-methoxypropionamide ((S)-lacosamide; (S)-LCM) which (i) decreased sEPSC frequency, (ii) increased paired-pulse ratio, and (iii) reduced the presynaptic distribution of CaV2.2 and NaV1.7, two voltage-gated ion channels implicated in nociceptive signaling. (S)-LCM also inhibited depolarization-evoked release of the pro-nociceptive neurotransmitter calcitonin gene-related peptide (CGRP) in the spinal cord. Increased CRMP2 phosphorylation in rats with spared nerve injury (SNI) was decreased by intrathecal administration of (S)-LCM resulting in a loss of presynaptic localization of CaV2.2 and NaV1.7. Together, these findings indicate that CRMP2 regulates presynaptic excitatory neurotransmission in spinal cord and may play an important role in regulating pathological pain. Novel targeting strategies to inhibit CRMP2 phosphorylation by Cdk5 may have great potential for the treatment of chronic pain.
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