Specific roles for DEG/ENaC and TRP channels in touch and thermosensation in C. elegans nociceptors.
Polymodal nociceptors detect noxious stimuli, including harsh touch, toxic chemicals and extremes of heat and cold. The molecular mechanisms by which nociceptors are able to sense multiple qualitatively distinct stimuli are not well understood. We found that the C. elegans PVD neurons are mulitidendritic nociceptors that respond to harsh touch and cold temperatures. The harsh touch modality specifically required the DEG/ENaC proteins MEC-10 and DEGT-1, which represent putative components of a harsh touch mechanotransduction complex. In contrast, responses to cold required the TRPA-1 channel and were MEC-10 and DEGT-1 independent. Heterologous expression of C. elegans TRPA-1 conferred cold responsiveness to other C. elegans neurons and to mammalian cells, indicating that TRPA-1 is a cold sensor. Our results suggest that C. elegans nociceptors respond to thermal and mechanical stimuli using distinct sets of molecules and identify DEG/ENaC channels as potential receptors for mechanical pain.
Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge, UK.
Marios
M
Chatzigeorgiou
Sungjae
S
Yoo
Joseph D
JD
Watson
Wei-Hsiang
WH
Lee
W Clay
WC
Spencer
Katie S
KS
Kindt
Sun Wook
SW
Hwang
David M
DM
Miller
Millet
M
Treinin
Monica
M
Driscoll
William R
WR
Schafer
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology*; D053503:Epithelial Sodium Channels / Q000378:metabolism / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000145:classification; D009619:Nociceptors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology*; D013697:Thermosensing / Q000502:physiology; D014110:Touch / Q000502:physiology; D050051:Transient Receptor Potential Channels / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C094927:Deg-1 protein, C elegans; D053503:Epithelial Sodium Channels; D008565:Membrane Proteins; D015222:Sodium Channels; D050051:Transient Receptor Potential Channels; C085942:MEC-10 protein, C elegans