1.A.17.4.7
The sodium sensor/cation conductance channel activated by high extracellular Na⁺, Tmc-1 (Tmc1) (Chatzigeorgiou et al. 2013).  It functions in salt taste chemosensation and salt avoidance and is an ionotropic sensory receptor.  Wang et al. 2016 showed that C. elegans TMC-1 mediates nociceptor responses to high pH, not sodium, allowing the nematode to avoid strongly alkaline environments in which most animals cannot survive (Spalthoff and Göpfert 2016).  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). TMC-1 is necessary for sodium attraction, but not aversion in the nematode. Dao et al. 2020 showed that TMC-1 contributes to the nematode's lithium induced attraction behavior, but not potassium or magnesium attraction, thus clarifying the specificity of the response. In addition, they found that sodium conditioned aversion is dependent on TMC-1 and disrupts both sodium- and lithium-induced attraction (Dao et al. 2020). The C. elegans Tmc-1 is involved in egg-laying inhibition in response to harsh touch (Kaulich et al. 2021). The initial step in the sensory transduction pathway underpinning hearing and balance in mammals involves the conversion of force into the gating of a mechanosensory transduction channel. Jeong et al. 2022 reported the single-particle cryo-EM structure of TMC-1 from C. elegans. The two-fold symmetric complex is composed of two copies each of the pore-forming TMC-1 subunit, the calcium-binding protein CALM-1 and the transmembrane inner ear protein TMIE. CALM-1 (see TC# 8.A.82.1.1) makes contacts with the cytoplasmic face of the TMC-1 subunits, whereas the single-pass TMIE subunits (see TC# 8.A.116) reside on the periphery of the complex, poised like the handles of an accordion. A subset of complexes  includes a single arrestin-like protein, arrestin domain protein (ARRD-6; see TC# 8.A.136.1.15), bound to a CALM-1 subunit. Single-particle reconstructions and molecular dynamics simulations showed how the mechanosensory transduction complex deforms the membrane bilayer to suggest roles for lipid-protein interactions in the mechanism by which mechanical force is transduced to ion channel gating (Jeong et al. 2022).