ArticleProceedings of the National Academy of Sciences of the United States of America2020
A paradigm of thermal adaptation in penguins and elephants by tuning cold activation in TRPM8.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 71 citations in OpenAlex.
- A single-point mutation in TRPA1 drives heat resilience in oviparous embryos.Science advances · 2026Article
- Molecular basis for cold and menthol sensing by mammalian TRPM8.Nature communications · 2026Article
- Decreased cold-sensing function of the transient receptor potential channel TRPM8 from tailed amphibians.FEBS open bio · 2026Article
- Sensing Underwater: Diversifying Selection, Convergent Evolution and Inactivation in Sensory Receptors' Genes of Aquatic Mammals.Journal of molecular evolution · 2026Article
- Conformational Fingerprints Underlying Thermal Modulation of PAC/TMEM206 Gating.International journal of molecular sciences · 2026Article
- Structural energetics of cold sensitivity.Nature · 2026Article
- Deep mutational scan of the pore of the cold-sensing TRPM8 channel.bioRxiv : the preprint server for biology · 2026Article
- TRPtracker: a community database for monitoring praziquantel sensitivity at TRPMInternational journal for parasitology. Drugs and drug resistance · 2026Article
- Understanding animal temperature sensation: from molecular thermosensors to physiological impacts.Science China. Life sciences · 2026Review
- Temperature-induced structural changes in thermosensitive transient receptor potential channels (thermoTRPs).Frontiers in molecular neuroscience · 2026Review
- Rational tuning of temperature sensitivity of the TRPM8 channel.EMBO reports · 2025Article
- ZNF334 truncation mutation drives cold-induced autoinflammation.EMBO molecular medicine · 2025Article
- A proton-gated channel identified in the centipede antenna.EMBO reports · 2025Article
- TRPtracker: a community database for monitoring praziquantel sensitivity at TRPMbioRxiv : the preprint server for biology · 2025Article
- The structural basis of cold sensitivity.bioRxiv : the preprint server for biology · 2025Article
- Conformational changes in heat- and proton-sensing ion channel in centipedes.Nature structural & molecular biology · 2025Article
- Article
- Genetic Code Expansion: Recent Developments and Emerging Applications.Chemical reviews · 2025Review
- Residues of TRPM8 at the Lipid-Water-Interface have Coevolved with Cholesterol Interaction and are Relevant for Diverse Health Disorders.The Journal of membrane biology · 2024Article
- Across two continents: The genomic basis of environmental adaptation in house mice (Mus musculus domesticus) from the Americas.PLoS genetics · 2024Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To adapt to habitat temperature, vertebrates have developed sophisticated physiological and ecological mechanisms through evolution. Transient receptor potential melastatin 8 (TRPM8) serves as the primary sensor for cold. However, how cold activates TRPM8 and how this sensor is tuned for thermal adaptation remain largely unknown. Here we established a molecular framework of how cold is sensed in TRPM8 with a combination of patch-clamp recording, unnatural amino acid imaging, and structural modeling. We first observed that the maximum cold activation of TRPM8 in eight different vertebrates (i.e., African elephant and emperor penguin) with distinct side-chain hydrophobicity (SCH) in the pore domain (PD) is tuned to match their habitat temperature. We further showed that altering SCH for residues in the PD with solvent-accessibility changes leads to specific tuning of the cold response in TRPM8. We also observed that knockin mice expressing the penguin's TRPM8 exhibited remarkable tolerance to cold. Together, our findings suggest a paradigm of thermal adaptation in vertebrates, where the evolutionary tuning of the cold activation in the TRPM8 ion channel through altering SCH and solvent accessibility in its PD largely contributes to the setting of the cold-sensitive/tolerant phenotype.
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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.