ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Cyclin-dependent kinase 5 controls TRPV1 membrane trafficking and the heat sensitivity of nociceptors through KIF13B.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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56 citing papers in PubMed, 93 citations in OpenAlex.
- Microtubule Cytoskeleton Dysfunction in Chronic Pain: Mechanisms of Transport Failure and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- The Recycling Endosomal (NaActa physiologica (Oxford, England) · 2026Article
- Calpain cleaves the distal carboxyl terminus of TRPV1 and modulates its tachyphylaxis.Cell & bioscience · 2026Article
- KIF13B Attenuates Sepsis-Induced Myocardial Dysfunction through the Stabilization of PLIN5.Research (Washington, D.C.) · 2026Article
- Cdk5 modulates orofacial pain through P2X2/3 purinergic receptor-mediated signaling in trigeminal neurons.Frontiers in pharmacology · 2026Article
- TAT-T407 Mitigates Apoptosis and Cognitive Impairments Following Cerebral Ischemia Through Disruption of TRPV1-CDK5 Interaction.Molecular neurobiology · 2025Article
- Article
- Genetic code expansion, click chemistry, and light-activated PI3K reveal details of membrane protein trafficking downstream of receptor tyrosine kinases.bioRxiv : the preprint server for biology · 2024Article
- Endophilin A2 controls touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking.Military Medical Research · 2024Article
- The role of PAR2 in regulating MIF release in house dust mite-induced atopic dermatitis.Frontiers in immunology · 2024Article
- Inhibitions and Down-Regulation of Motor Protein Eg5 Expression in Primary Sensory Neurons Reveal a Novel Therapeutic Target for Pathological Pain.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Nociceptive signaling through transient receptor potential vanilloid 1 is regulated by Cyclin Dependent Kinase 5-mediated phosphorylation of T407 in vivo.Molecular pain · 2022Article
- Modulation of KIF17/NR2B crosstalk by tozasertib attenuates inflammatory pain in rats.Inflammopharmacology · 2022Article
- Visualization of trigeminal ganglion sensory neuronal signaling regulated by Cdk5.Cell reports · 2022Article
- Phosphoregulation of Kinesins Involved in Long-Range Intracellular Transport.Frontiers in cell and developmental biology · 2022Review
- Inducible manipulation of motor-cargo interaction using engineered kinesin motors.Journal of cell science · 2021Article
- ATF4 selectively regulates heat nociception and contributes to kinesin-mediated TRPM3 trafficking.Nature communications · 2021Article
- Article
- Distribution and Assembly of TRP Ion Channels.Advances in experimental medicine and biology · 2021Article
- Site-specific contacts enable distinct modes of TRPV1 regulation by the potassium channel Kvβ1 subunit.The Journal of biological chemistry · 2020Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The number of functional transient receptor potential vanilloid 1 (TRPV1) channels at the surface, especially at the peripheral terminals of primary sensory neurons, regulates heat sensitivity, and increased surface localization of TRPV1s contributes to heat hyperalgesia. However, the mechanisms for regulating TRPV1 surface localization are essentially unknown. Here, we show that cyclin-dependent kinase 5 (Cdk5), a new player in thermal pain sensation, positively regulates TRPV1 surface localization. Active Cdk5 was found to promote TRPV1 anterograde transport in vivo, suggesting a regulatory role of Cdk5 in TRPV1 membrane trafficking. TRPV1-containing vesicles bind to the forkhead-associated (FHA) domain of the KIF13B (kinesin-3 family member 13B) and are thus delivered to the cell surface. Overexpression of Cdk5 or its activator p35 promoted and inhibition of Cdk5 activity prevented the KIF13B-TRPV1 association, indicating that Cdk5 promotes TRPV1 anterograde transport by mediating the motor-cargo association. Cdk5 phosphorylates KIF13B at Thr-506, a residue located in the FHA domain. T506A mutation reduced the motor-cargo interaction and the cell-permeable TAT-T506 peptide, targeting to the Thr-506, decreased TRPV1 surface localization, demonstrating the essential role of Thr-506 phosphorylation in TRPV1 transport. Moreover, complete Freund's adjuvant (CFA) injection-induced activation of Cdk5 increased the anterograde transport of TRPV1s, contributing to the development and possibly the maintenance of heat hyperalgesia, whereas intrathecal delivery of the TAT-T506 peptide alleviated CFA-induced heat hyperalgesia in rats. Thus, Cdk5 regulation of TRPV1 membrane trafficking is a fundamental mechanism controlling the heat sensitivity of nociceptors, and moderate inhibition of Thr-506 phosphorylation during inflammation might be helpful for the treatment of inflammatory thermal pain.
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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.