1.A.17.4.8
Tmc2 channel of 1203 aas and 9 - 11 TMSs; functions in touch neurons as a mechanosensitive touch sensor (Chatzigeorgiou et al. 2013; WR Schafer, personal communication).  May function as a Na⁺/K⁺ channel.  TMC-1 and TMC-2 are required for normal egg laying in C. elegans. Mutations in these proteins cause membrane hyperpolarization and disrupt the rhythmic calcium activities in both neurons and muscles involved in egg laying. Mechanistically, TMC proteins enhance membrane depolarization through background leak currents, and ectopic expression of both C. elegans and mammalian TMC proteins results in membrane depolarization (Yue et al. 2018).  The structure of the C. elegans TMC-2 complex suggests roles of lipid-mediated subunit contacts in mechanosensory transduction (Clark et al. 2023).  The complex is composed of two copies of the pore-forming TMC-2 subunit, the calcium and integrin binding protein CALM-1 and the transmembrane inner ear protein TMIE. Comparison of the TMC-2 complex to the recently published cryo-EM structure of the C. elegans TMC-1 complex highlights conserved protein-lipid interactions, as well as a pi-helical structural motif in the pore-forming helices, that together suggest a mechanism for TMC-mediated mechanosensory transduction (Clark et al. 2024).  TMC ion channels are expressed throughout the animal kingdom. Mammals express eight TMCs (mTMC1-8), two of which (mTMC1 and mTMC2) are subunits of mechanotransduction channels (Jiang et al. 2024). C. elegans expresses TMC-1 and TMC-2, which mediate mechanosensation, egg laying, and alkaline sensing. Association with accessory proteins tunes nematode TMC-1 to divergent sensory functions, and distinct TMC-1 domains enable touch and alkaline sensing. These domains are segregated in mammals between mTMC1 and mTMC3. Consistent with these findings, mammalian mTMC1 can mediate mechanosensation in nematodes, while mTMC3 can mediate alkaline sensation. Thus, sequence diversification and association with accessory proteins has led to the emergence of TMC protein complexes with diverse properties and physiological functions (Jiang et al. 2024).  The structure of the Caenorhabditis elegans TMC-2 complex suggests roles of lipid-mediated subunit contacts in mechanosensory transduction (Clark et al. 2024).