The mechanosensory protein MEC-6 is a subunit of the C. elegans touch-cell degenerin channel.
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.
Chelur
Dattananda S
DS
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Ernstrom
Glen G
GG
Goodman
Miriam B
MB
Yao
C Andrea
CA
Chen
Lei
L
O' Hagan
Robert
R
Chalfie
Martin
M
D000818:Animals; D043303:Aryldialkylphosphatase; D001369:Axons / Q000737:chemistry; D016466:CHO Cells; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D006224:Cricetinae; D004553:Electric Conductivity; D017238:Genes, Helminth / Q000235:genetics; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D008465:Mechanoreceptors / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D021381:Protein Transport; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D013489:Suppression, Genetic / Q000235:genetics; D014110:Touch / Q000502:physiology*; D014982:Xenopus laevis
D029742:Caenorhabditis elegans Proteins; C094927:Deg-1 protein, C elegans; D015801:Helminth Proteins; C096705:MEC-2 protein, C elegans; C115871:Mec-4 protein, C elegans; D008565:Membrane Proteins; D021122:Protein Subunits; D015222:Sodium Channels; C085942:MEC-10 protein, C elegans; D012964:Sodium; C470181:MEC-6 protein, C elegans; D043303:Aryldialkylphosphatase