ArticleProceedings of the National Academy of Sciences of the United States of America2022
The acquisition of cold sensitivity during TRPM8 ion channel evolution.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- A single-point mutation in TRPA1 drives heat resilience in oviparous embryos.Science advances · 2026Article
- Sensing Underwater: Diversifying Selection, Convergent Evolution and Inactivation in Sensory Receptors' Genes of Aquatic Mammals.Journal of molecular evolution · 2026Article
- Decreased cold-sensing function of the transient receptor potential channel TRPM8 from tailed amphibians.FEBS open bio · 2026Article
- Deep mutational scan of the pore of the cold-sensing TRPM8 channel.bioRxiv : the preprint server for biology · 2026Article
- Evolution in metazoans of the TRPM channel family involves multiple gains and losses of genes and domains.Molecular biology and evolution · 2026Article
- Understanding animal temperature sensation: from molecular thermosensors to physiological impacts.Science China. Life sciences · 2026Review
- Structural basis for agonist and heat activation of nociceptor TRPM3.Nature structural & molecular biology · 2026Article
- TRP Channels from Sensory Coding to Physiology.Metabolites · 2025Review
- Cold- and TRPM8-dependent shaking in mammals and birds.Communications biology · 2025Article
- A proton-gated channel identified in the centipede antenna.EMBO reports · 2025Article
- Rational tuning of temperature sensitivity of the TRPM8 channel.EMBO reports · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Evolutionary adaptations of TRPA1 thermosensitivity and skin thermoregulation in vertebrates.iScience · 2025Article
- 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
- Article
- Ion channels of cold transduction and transmission.The Journal of general physiology · 2024Review
- Conservation of the cooling agent binding pocket within the TRPM subfamily.bioRxiv : the preprint server for biology · 2024Article
- Vertebrate behavioral thermoregulation: knowledge and future directions.Neurophotonics · 2024Review
- Evidence that the cold- and menthol-sensing functions of the human TRPM8 channel evolved separately.Science advances · 2024Article
- Use the force, fluke: Ligand-independent gating of Schistosoma mansoni ion channel TRPMInternational journal for parasitology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To cope with temperature fluctuations, molecular thermosensors in animals play a pivotal role in accurately sensing ambient temperature. Transient receptor potential melastatin 8 (TRPM8) is the most established cold sensor. In order to understand how the evolutionary forces bestowed TRPM8 with cold sensitivity, insights into both emergence of cold sensing during evolution and the thermodynamic basis of cold activation are needed. Here, we show that the trpm8 gene evolved by forming and regulating two domains (MHR1-3 and pore domains), thus determining distinct cold-sensitive properties among vertebrate TRPM8 orthologs. The young trpm8 gene without function can be observed in the closest living relatives of tetrapods (lobe-finned fishes), while the mature MHR1-3 domain with independent cold sensitivity has formed in TRPM8s of amphibians and reptiles to enable channel activation by cold. Furthermore, positive selection in the TRPM8 pore domain that tuned the efficacy of cold activation appeared late among more advanced terrestrial tetrapods. Interestingly, the mature MHR1-3 domain is necessary for the regulatory mechanism of the pore domain in TRPM8 cold activation. Our results reveal the domain-based evolution for TRPM8 functions and suggest that the acquisition of cold sensitivity in TRPM8 facilitated terrestrial adaptation during the water-to-land transition.
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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.