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.
Chatzigeorgiou
Marios
M
Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge, UK.
Yoo
Sungjae
S
Watson
Joseph D
JD
Lee
Wei-Hsiang
WH
Spencer
W Clay
WC
Kindt
Katie S
KS
Hwang
Sun Wook
SW
Miller
David M
DM
Treinin
Millet
M
Driscoll
Monica
M
Schafer
William R
WR
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