tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans

Nature. 2013 Feb 7;494(7435):95-99. doi: 10.1038/nature11845. Epub 2013 Jan 30.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / drug effects
  • CHO Cells
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / physiology*
  • Cricetinae
  • Electric Conductivity
  • Ion Channels / agonists
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Osmolar Concentration
  • Sodium Chloride / metabolism*
  • Sodium Chloride / pharmacology
  • Taste / drug effects
  • Taste / physiology*

Substances

  • Ion Channels
  • TMC-1 protein, C elegans
  • Sodium Chloride