TMC6 functions as a GPCR-like receptor to sense noxious heat via Gαq signaling.

ABSTRACT: Thermosensation is vital for the survival, propagation, and adaption of all organisms, but its mechanism is not fully understood yet. Here, we find that TMC6, a membrane protein of unknown function, is highly expressed in dorsal root ganglion (DRG) neurons and functions as a Gαq-coupled G protein-coupled receptor (GPCR)-like receptor to sense noxious heat. TMC6-deficient mice display a substantial impairment in noxious heat sensation while maintaining normal perception of cold, warmth, touch, and mechanical pain. Further studies show that TMC6 interacts with Gαq via its intracellular C-terminal region spanning Ser⁷⁸⁰ to Pro⁸¹⁰. Specifically disrupting such interaction using polypeptide in DRG neurons, genetically ablating Gαq, or pharmacologically blocking Gαq-coupled

SUBMITTER: Zhang C 

PROVIDER: S-EPMC11183229 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature