ArticleScience advances2024
Mechanisms of sensory adaptation and inhibition of the cold and menthol receptor TRPM8.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Bioinspired supramolecular thermistor for resolving subtle temperature variations.Science advances · 2026Article
- Molecular basis for cold and menthol sensing by mammalian TRPM8.Nature communications · 2026Article
- Symmetry-driven gating of TRPM8 by PIPNature communications · 2026Article
- Temperature-Dependent Menthol Binding across TRPM8 Conformational States.Journal of the American Chemical Society · 2026Article
- Structural mechanism of Necrocide 1 activation of human TRPM4 that triggers necrosis by sodium overload.Nature communications · 2026Article
- Review
- Deep mutational scan of the pore of the cold-sensing TRPM8 channel.bioRxiv : the preprint server for biology · 2026Article
- Structural energetics of cold sensitivity.Nature · 2026Article
- TRPA1 and TRPM8 in Allergic Rhinitis and Chronic Rhinosinusitis: Emerging Role in Neuroimmune Inflammation.Biomedicines · 2026Review
- Structural mechanism of Necrocide 1 activation of human TRPM4 that triggers necrosis by sodium overload.bioRxiv : the preprint server for biology · 2026Article
- 5'untranslated regions provide a versatile toolkit for tunable exogenous protein expression.Molecular biology of the cell · 2026Article
- A single allosteric site merges activation, modulation and inhibition in TRPM5.Nature chemical biology · 2026Article
- Review
- Structural landscape of activation, desensitization and inhibition in the human TRPM4 channel.Nature structural & molecular biology · 2026Article
- The structural basis of cold sensitivity.bioRxiv : the preprint server for biology · 2025Article
- TRPM8 Protein Dynamics Correlates with Ligand Structure and Cellular Function.Journal of the American Chemical Society · 2025Article
- Molecular basis of the urate transporter URAT1 inhibition by gout drugs.Nature communications · 2025Article
- TRPM8 protein dynamics correlates with ligand structure and cellular function.bioRxiv : the preprint server for biology · 2025Article
- Menthol in Livestock: Unveiling Its Multifaceted Properties and Future Potential for Sustainable Agriculture.International journal of molecular sciences · 2025Review
- Forty sites of TRP channel regulation.Current opinion in chemical biology · 2025Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Our sensory adaptation to cold and chemically induced coolness is mediated by the intrinsic property of TRPM8 channels to desensitize. TRPM8 is also implicated in cold-evoked pain disorders and migraine, highlighting its inhibitors as an avenue for pain relief. Despite the importance, the mechanisms of TRPM8 desensitization and inhibition remained unclear. We found, using cryo-electron microscopy, electrophysiology, and molecular dynamics simulations, that TRPM8 inhibitors bind selectively to the desensitized state of the channel. These inhibitors were used to reveal the overlapping mechanisms of desensitization and inhibition and that cold and cooling agonists share a common desensitization pathway. Furthermore, we identified the structural determinants crucial for the conformational change in TRPM8 desensitization. Our study illustrates how receptor-level conformational changes alter cold sensation, providing insights into therapeutic development.
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