The mechanosensory protein MEC-6 is a subunit of the C. elegans touch-cell degenerin channel

Nature. 2002 Dec 12;420(6916):669-73. doi: 10.1038/nature01205.

Abstract

Mechanosensory transduction in touch receptor neurons is believed to be mediated by DEG/ENaC (degenerin/epithelial Na+ channel) proteins in nematodes and mammals. In the nematode Caenorhabditis elegans, gain-of-function mutations in the degenerin genes mec-4 and mec-10 (denoted mec-4(d) and mec-10(d), respectively) cause degeneration of the touch cells. This phenotype is completely suppressed by mutation in a third gene, mec-6 (refs 3, 4), that is needed for touch sensitivity. This last gene is also required for the function of other degenerins. Here we show that mec-6 encodes a single-pass membrane-spanning protein with limited similarity to paraoxonases, which are implicated in human coronary heart disease. This gene is expressed in muscle cells and in many neurons, including the six touch receptor neurons. MEC-6 increases amiloride-sensitive Na+ currents produced by MEC-4(d)/MEC-10(d) by approximately 30-fold, and functions synergistically with MEC-2 (a stomatin-like protein that regulates MEC-4(d)/MEC-10(d) channel activity) to increase the currents by 200-fold. MEC-6 physically interacts with all three channel proteins. In vivo, MEC-6 co-localizes with MEC-4, and is required for punctate MEC-4 expression along touch-neuron processes. We propose that MEC-6 is a part of the degenerin channel complex that may mediate mechanotransduction in touch cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aryldialkylphosphatase
  • Axons / chemistry
  • CHO Cells
  • Caenorhabditis elegans / chemistry
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cloning, Molecular
  • Cricetinae
  • Electric Conductivity
  • Genes, Helminth / genetics
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism
  • Ion Channel Gating / drug effects
  • Mechanoreceptors / chemistry*
  • Mechanoreceptors / cytology
  • Mechanoreceptors / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Subunits
  • Protein Transport
  • Sodium / metabolism
  • Sodium Channels / chemistry*
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Substrate Specificity
  • Suppression, Genetic / genetics
  • Touch / physiology*
  • Xenopus laevis

Substances

  • Caenorhabditis elegans Proteins
  • Deg-1 protein, C elegans
  • Helminth Proteins
  • MEC-2 protein, C elegans
  • Mec-4 protein, C elegans
  • Membrane Proteins
  • Protein Subunits
  • Sodium Channels
  • MEC-10 protein, C elegans
  • Sodium
  • MEC-6 protein, C elegans
  • Aryldialkylphosphatase