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Drosophila NOMPC is a mechanotransduction channel subunit for gentle-touch sensation

Abstract

Touch sensation is essential for behaviours ranging from environmental exploration to social interaction; however, the underlying mechanisms are largely unknown1. In Drosophila larvae, two types of sensory neurons, class III and class IV dendritic arborization neurons, tile the body wall. The mechanotransduction channel PIEZO in class IV neurons is essential for sensing noxious mechanical stimuli but is not involved in gentle touch2. On the basis of electrophysiological-recording, calcium-imaging and behavioural studies, here we report that class III dendritic arborization neurons are touch sensitive and contribute to gentle-touch sensation. We further identify NOMPC (No mechanoreceptor potential C), a member of the transient receptor potential (TRP) family of ion channels, as a mechanotransduction channel for gentle touch. NOMPC is highly expressed in class III neurons and is required for their mechanotransduction. Moreover, ectopic NOMPC expression confers touch sensitivity to the normally touch-insensitive class IV neurons. In addition to the critical role of NOMPC in eliciting gentle-touch-mediated behavioural responses, expression of this protein in the Drosophila S2 cell line also gives rise to mechanosensitive channels in which ion selectivity can be altered by NOMPC mutation, indicating that NOMPC is a pore-forming subunit of a mechanotransduction channel. Our study establishes NOMPC as a bona fide mechanotransduction channel that satisfies all four criteria proposed for a channel to qualify as a transducer of mechanical stimuli3 and mediates gentle-touch sensation. Our study also suggests that different mechanosensitive channels may be used to sense gentle touch versus noxious mechanical stimuli.

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Figure 1: NOMPC is required for mechanotransduction of class III dendritic arborization neurons that function in gentle-touch sensation of larvae.
Figure 2: Ectopic NOMPC expression confers mechanosensitivity to the normally touch-insensitive class IV dendritic arborization neurons.
Figure 3: Heterologous expression of NOMPC in S2 cells yields mechanosensitive channels.
Figure 4: NOMPC is likely a pore-forming subunit of the mechanotransduction channel.

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Acknowledgements

We thank C. Zuker, U. Heberlein, G. Rubin, T. Lee and R. Bodmer for fly lines, J. Howard for the NOMPC antibody and L. Looger for GCaMP5. We thank D. Minor and S. Bagriantsev for assistance with the high-speed pressure clamp. We thank S. Younger, S. Barbel and T. Cheng for technical support, W. P. Ge, M. P. Klassen, P. Fan, E. K. Unger and C. J. Peters for reading the manuscript, and members of the Jan laboratory for discussion. Z.Y. and Y.X. are recipients of the Long-Term Fellowship from the Human Frontier Science Program. This work was supported by National Institutes of Health grants (R37NS040929 and 5R01MH084234) to Y.N.J. L.Y.J. and Y.N.J. are investigators of the Howard Hughes Medical Institute.

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Z.Y. and W.Z. initiated the project, designed and conducted most experiments; Y.N.J. and L.Y.J. supervised the project and provided guidance throughout. L.E.C. and W.Z. made the NOMPC mutants. Y.H., Y.X. and S.M. assisted with part of the behavioural experiments and immunostaining. D.G. helped set up the piezo actuator system. Z.Y., W.Z., L.Y.J. and Y.N.J. wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Yuh Nung Jan.

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The authors declare no competing financial interests.

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Yan, Z., Zhang, W., He, Y. et al. Drosophila NOMPC is a mechanotransduction channel subunit for gentle-touch sensation. Nature 493, 221–225 (2013). https://doi.org/10.1038/nature11685

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