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Specific roles for DEG/ENaC and TRP channels in touch and thermosensation in C. elegans nociceptors

Abstract

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.

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Figure 1: PVD neurons respond to harsh touch and cold temperature.
Figure 2: mec-10 is required for harsh touch in PVD.
Figure 3: DEGT-1 is required for harsh touch responses in PVD.
Figure 4: Localization patterns of DEGT-1 and MEC-10 fusion proteins in PVD.
Figure 5: Effect of mec-10 on harsh touch responses in ALM.
Figure 6: TRPA-1 is specifically required for cold responses in PVD.
Figure 7: Heterologous expression of TRPA-1 in C. elegans neurons confers cold sensitivity.
Figure 8: Cold stimuli activate TRPA-1–expressing HEK293T cells.

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Acknowledgements

We thank the Caenorhabditis Genetics Center, the National Bioresource Project and the Mitani laboratory for worm strains, N. Barry for help with microscopy, I. Rabinowitz for writing software to analyze averaged ratio traces, D. Cattermole and P. Heard in the LMB technical workshop for designing and building thermal controllers, the Vanderbilt Functional Genomics Shared Resource for help with microarray experiments and R. Branicky for comments on the manuscript. This research was supported by the Medical Research Council and grants from the National Institute on Drug Abuse (W.R.S.) and the National Institute of Neurological Disorders and Stroke (M.D. and D.M.M.), from the Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology of Korea (code M103KV010015-06K2201-01510) and National Research Foundation of Korea (codes KRF-2008-331-E00457 and 2009-0076543) to S.W.H., and from the US-Israel Binational Science Foundation (grant 2005036 to M.T. and D.M.M.).

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Unless otherwise noted, experiments were conducted and analyzed by M.C. under the guidance of W.R.S. Mammalian TRPA-1 expression and electrophysiology experiments were conducted by S.Y. under the guidance of S.W.H. J.D.W. generated the microarry data for PVD expression profiling using an mRNA tagging strain constructed by W.C.S. D.M.M. and M.T. supervised this work and helped with analysis. M.T. first observed the nociceptor-like morphology of PVD. K.S.K. generated the cameleon line for PVD and FLP imaging. W.-H.L. initially characterized the harsh touch behavior of mec-10 and generated the mec-10 mec-4 double mutants under the guidance of M.D. W.R.S. wrote the paper with feedback from the other authors.

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Correspondence to William R Schafer.

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Chatzigeorgiou, M., Yoo, S., Watson, J. et al. Specific roles for DEG/ENaC and TRP channels in touch and thermosensation in C. elegans nociceptors. Nat Neurosci 13, 861–868 (2010). https://doi.org/10.1038/nn.2581

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