ArticleScientific reports2016
TRPV1 function is modulated by Cdk5-mediated phosphorylation: insights into the molecular mechanism of nociception.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- The Recycling Endosomal (NaActa physiologica (Oxford, England) · 2026Article
- Cdk5 modulates orofacial pain through P2X2/3 purinergic receptor-mediated signaling in trigeminal neurons.Frontiers in pharmacology · 2026Article
- Pathway-dependent cold activation of heat-responsive TRPV channels.Scientific reports · 2025Article
- TAT-T407 Mitigates Apoptosis and Cognitive Impairments Following Cerebral Ischemia Through Disruption of TRPV1-CDK5 Interaction.Molecular neurobiology · 2025Article
- Palmitoylation by ZDHHC4 inhibits TRPV1-mediated nociception.EMBO reports · 2025Article
- The Endocannabinoid Peptide RVD-Hemopressin Is a TRPV1 Channel Blocker.Biomolecules · 2024Article
- Resiniferatoxin: Nature's Precision Medicine to Silence TRPV1-Positive Afferents.International journal of molecular sciences · 2023Review
- Mutagenesis studies of TRPV1 subunit interfaces informed by genomic variant analysis.Biophysical journal · 2023Article
- Cdk5 regulates IP3R1-mediated CaCellular and molecular life sciences : CMLS · 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
- Visualization of trigeminal ganglion sensory neuronal signaling regulated by Cdk5.Cell reports · 2022Article
- Review
- Effects of non-euphoric plant cannabinoids on muscle quality and performance of dystrophic mdx mice.British journal of pharmacology · 2019Article
- Phosphorylation of the Transient Receptor Potential Ankyrin 1 by Cyclin-dependent Kinase 5 affects Chemo-nociception.Scientific reports · 2018Article
- H89 dihydrochloride hydrate and calphostin C lower the body temperature through TRPV1.Molecular medicine reports · 2018Article
- TNF-α Increases Production of Reactive Oxygen Species through Cdk5 Activation in Nociceptive Neurons.Frontiers in physiology · 2018Article
- Modulation of TRPA1 channel activity by Cdk5 in sensory neurons.Channels (Austin, Tex.) · 2018Article
- Article
- Signatures of Altered Gene Expression in Dorsal Root Ganglia of a Fabry Disease Mouse Model.Frontiers in molecular neuroscience · 2017Article
- Toward elucidating the heat activation mechanism of the TRPV1 channel gating by molecular dynamics simulation.Proteins · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
TRPV1 is a polymodally activated cation channel acting as key receptor in nociceptive neurons. Its function is strongly affected by kinase-mediated phosphorylation leading to hyperalgesia and allodynia. We present behavioral and molecular data indicating that TRPV1 is strongly modulated by Cdk5-mediated phosphorylation at position threonine-407(mouse)/T406(rat). Increasing or decreasing Cdk5 activity in genetically engineered mice has severe consequences on TRPV1-mediated pain perception leading to altered capsaicin consumption and sensitivity to heat. To understand the molecular and structural/functional consequences of TRPV1 phosphorylation, we generated various rTRPV1T406 receptor variants to mimic phosphorylated or dephosphorylated receptor protein. We performed detailed functional characterization by means of electrophysiological whole-cell and single-channel recordings as well as Ca(2+)-imaging and challenged recombinant rTRPV1 receptors with capsaicin, low pH, or heat. We found that position T406 is critical for the function of TRPV1 by modulating ligand-sensitivity, activation, and desensitization kinetics as well as voltage-dependence. Based on high resolution structures of TRPV1, we discuss T406 being involved in the molecular transition pathway, its phosphorylation leading to a conformational change and influencing the gating of the receptor. Cdk5-mediated phosphorylation of T406 can be regarded as an important molecular switch modulating TRPV1-related behavior and pain sensitivity.
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Registered trials
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.