tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans
- 30 January 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 494 (7435), 95-99
- https://doi.org/10.1038/nature11845
Abstract
The membrane protein TMC-1 is required for salt avoidance behaviour in C. elegans, functions as an ion channel directly activated by NaCl in vitro and is a candidate salt chemosensor; the human homologue of TMC-1 is linked to deafness and may be the cochlear hair-cell mechanotransduction channel. Receptors have been identified for bitterness, sweetness and umami tastes, but not definitively for saltiness and sourness. Bill Schafer, Sun Wook Hwang and their teams find that the membrane protein TMC-1 is required for salt-aversion behaviour in the roundworm Caenorhabditis elegans, and show that it acts as an ion channel directly activated by sodium chloride in vitro. The human homologue of TMC-1 is associated with deafness, and this work makes it an attractive candidate for the long-sought cochlear hair-cell mechanotransduction channel. Mammals contain several TMC proteins of unknown function, and it is possible that one or more of these may have a role in sensory transduction processes such as touch or salt taste. 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.Keywords
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