Back to Search
Start Over
The acquisition of cold sensitivity during TRPM8 ion channel evolution.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 5/24/2022, Vol. 119 Issue 21, p1-8. 25p. - Publication Year :
- 2022
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ION channels
*TETRAPODS
*AMPHIBIANS
*REPTILES
*VERTEBRATES
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 119
- Issue :
- 21
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 157096886
- Full Text :
- https://doi.org/10.1073/pnas.2201349119