tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans.
Transmembrane channel-like (TMC) genes encode a broadly conserved family of multipass integral membrane proteins in animals. 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 determined. 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.
Cell Biology Division, MRC Laboratory of Molecular Biology, Hills Road, Cambridge UK.
Marios
M
Chatzigeorgiou
Department of Biomedical Sciences, Korea University College of Medicine, Seoul 136-705, Korea.
Sangsu
S
Bang
Department of Biomedical Sciences, Korea University College of Medicine, Seoul 136-705, Korea.
Sun Wook
SW
Hwang
Cell Biology Division, MRC Laboratory of Molecular Biology, Hills Road, Cambridge UK.
William R
WR
Schafer
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D016466:CHO Cells; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D004553:Electric Conductivity; D007473:Ion Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D009994:Osmolar Concentration; D012965:Sodium Chloride / Q000378:metabolism* / Q000494:pharmacology; D013649:Taste / Q000187:drug effects / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins
D007473:Ion Channels; D012965:Sodium Chloride; C578678:TMC-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins