Transmembrane channel-like (TMC) genes encode a broadly conserved family of multipass integral membrane proteins in animals1,2. Human TMC1 and TMC2 genes are linked to human deafness and required for hair-cell mechanotransduction; however, the molecular functions of these and other TMC proteins have not been determined3,4,5,6. Here we show that the Caenorhabditis elegans tmc-1 gene encodes a sodium sensor that functions specifically in salt taste chemosensation. tmc-1 is expressed in the ASH polymodal avoidance neurons, where it is required for salt-evoked neuronal activity and behavioural avoidance of high concentrations of NaCl. However, tmc-1 has no effect on responses to other stimuli sensed by the ASH neurons including high osmolarity and chemical repellents, indicating a specific role in salt sensation. When expressed in mammalian cell culture, C. elegans TMC-1 generates a predominantly cationic conductance activated by high extracellular sodium but not by other cations or uncharged small molecules. Thus, TMC-1 is both necessary for salt sensation in vivo and sufficient to generate a sodium-sensitive channel in vitro, identifying it as a probable ionotropic sensory receptor.
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We thank the Caenorhabditis Genetics Center and M. de Bono for strains, and A. Patapoutian, J. R. Holt, J. Hao, B. Zhao, D. Miller and R. Branicky for suggestions and comments on the manuscript. This research was supported by the Medical Research Council (W.R.S.) and grants to S.W.H. from the National Research Foundation of Korea (2012000540) and Korea Health technology R&D Project of Ministry of Health & Welfare (A111373).
The authors declare no competing financial interests.
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Chatzigeorgiou, M., Bang, S., Hwang, S. et al. tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans. Nature 494, 95–99 (2013). https://doi.org/10.1038/nature11845
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