The acquisition of cold sensitivity during TRPM8 ion channel evolution

On these freezing days, the function of the TRPM8 channel, the main cold transducer in the somatosensory system, becomes relevant.

This channel is expressed in amphibians, reptiles, birds, and mammals; however, its response to temperature drops differs among species.

In this study, by constructing chimeras between TRPM8 orthologs that show marked differences in their cold-evoked responses, the authors identified two critical regions for TRPM8 activation by this stimulus: the MHR1-3 domain (within the N-terminus) and the pore region.

More importantly, sequence analysis and its functional correlation allow the authors to unravel the evolutionary changes that explain how TRPM8 has evolved as the main molecular entity involved in innocuous cold transduction in mammals.


Xiancui Lu, Zhihao Yao, Yunfei Wang, Chuanlin Yin, Jiameng Li, Longhui Chai, Wenqi Dong, Licheng Yuan, Ren Lai, and Shilong Yang