ArticleScience advances2024
Evidence that the cold- and menthol-sensing functions of the human TRPM8 channel evolved separately.
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 12 papers.
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Who cites it
12 citing papers in PubMed.
- Temperature-Dependent Menthol Binding across TRPM8 Conformational States.Journal of the American Chemical Society · 2026Article
- TRPtracker: a community database for monitoring praziquantel sensitivity at TRPMInternational journal for parasitology. Drugs and drug resistance · 2026Article
- Topological metrics as evolutionary and dynamical descriptors of conformational landscapes within protein families.PLoS computational biology · 2026Article
- Pharmacological tools to modulate ordered membrane domains and order-dependent protein function.Communications chemistry · 2026Article
- The cornea-trigeminal axis: potassium channels as master regulators of ocular surface homeostasis and sensory transduction.Frontiers in cell and developmental biology · 2026Review
- A protein dynamics-based deep learning model enhances predictions of fitness and epistasis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Pharmacological Tools to Modulate Ordered Membrane Domains and Order-Dependent Protein Function.bioRxiv : the preprint server for biology · 2025Article
- TRPtracker: a community database for monitoring praziquantel sensitivity at TRPMbioRxiv : the preprint server for biology · 2025Article
- TRPM8 Protein Dynamics Correlates with Ligand Structure and Cellular Function.Journal of the American Chemical Society · 2025Article
- Bryostatins 1 and 3 inhibit TRPM8 and modify TRPM8- and TRPV1-mediated lung epithelial cell responses to a proinflammatory stimulus via protein kinase C.Molecular pharmacology · 2025Article
- TRPM8 protein dynamics correlates with ligand structure and cellular function.bioRxiv : the preprint server for biology · 2025Article
- Small-Molecule Modulators of Lipid Raft Stability and Protein-Raft Partitioning.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Transient receptor potential melastatin 8 (TRPM8) is a temperature- and menthol-sensitive ion channel that contributes to diverse physiological roles, including cold sensing and pain perception. Clinical trials targeting TRPM8 have faced repeated setbacks predominantly due to the knowledge gap in unraveling the molecular underpinnings governing polymodal activation. A better understanding of the molecular foundations between the TRPM8 activation modes may aid the development of mode-specific, thermal-neutral therapies. Ancestral sequence reconstruction was used to explore the origins of TRPM8 activation modes. By resurrecting key TRPM8 nodes along the human evolutionary trajectory, we gained valuable insights into the trafficking, stability, and function of these ancestral forms. Notably, this approach unveiled the differential emergence of cold and menthol sensitivity over evolutionary time, providing a fresh perspective on complex polymodal behavior. These studies provide a paradigm for understanding polymodal behavior in TRPM8 and other proteins with the potential to enhance our understanding of sensory receptor biology and pave the way for innovative therapeutic interventions.
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