The role of Drosophila Piezo in mechanical nociception

Abstract

Transduction of mechanical stimuli by receptor cells is essential for senses such as hearing, touch and pain1,2,3,4. Ion channels have a role in neuronal mechanotransduction in invertebrates1; however, functional conservation of these ion channels in mammalian mechanotransduction is not observed. For example, no mechanoreceptor potential C (NOMPC), a member of transient receptor potential (TRP) ion channel family, acts as a mechanotransducer in Drosophila melanogaster5 and Caenorhabditis elegans6,7; however, it has no orthologues in mammals. Degenerin/epithelial sodium channel (DEG/ENaC) family members are mechanotransducers in C. elegans8 and potentially in D. melanogaster9; however, a direct role of its mammalian homologues in sensing mechanical force has not been shown. Recently, Piezo1 (also known as Fam38a) and Piezo2 (also known as Fam38b) were identified as components of mechanically activated channels in mammals10. The Piezo family are evolutionarily conserved transmembrane proteins. It is unknown whether they function in mechanical sensing in vivo and, if they do, which mechanosensory modalities they mediate. Here we study the physiological role of the single Piezo member in D. melanogaster (Dmpiezo; also known as CG8486). Dmpiezo expression in human cells induces mechanically activated currents, similar to its mammalian counterparts11. Behavioural responses to noxious mechanical stimuli were severely reduced in Dmpiezo knockout larvae, whereas responses to another noxious stimulus or touch were not affected. Knocking down Dmpiezo in sensory neurons that mediate nociception and express the DEG/ENaC ion channel pickpocket (ppk) was sufficient to impair responses to noxious mechanical stimuli. Furthermore, expression of Dmpiezo in these same neurons rescued the phenotype of the constitutive Dmpiezo knockout larvae. Accordingly, electrophysiological recordings from ppk-positive neurons revealed a Dmpiezo-dependent, mechanically activated current. Finally, we found that Dmpiezo and ppk function in parallel pathways in ppk-positive cells, and that mechanical nociception is abolished in the absence of both channels. These data demonstrate the physiological relevance of the Piezo family in mechanotransduction in vivo, supporting a role of Piezo proteins in mechanosensory nociception.

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Figure 1: Mechanical nociception defect in Dm piezo knockout larvae.
Figure 2: Dm piezo functions in ppk -positive type II sensory neurons.
Figure 3: Dm piezo mediates mechanically activated currents in ppk -positive neurons.
Figure 4: Dm piezo and ppk function in parallel pathways.

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Acknowledgements

We thank Y. N. Jan of the University of California San Francisco for providing ppk-EGFP5. Research was support by the National Institutes of Health and Novartis Research Foundation. S.E.K. and A.C. are supported by the Skaggs Institute.

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S.E.K. conducted most experiments. B. Coste performed the electrophysiology experiments shown in Fig. 3 and Supplementary Fig. 5. A.C. performed the fly electrophysiology experiments shown in Supplementary Fig. 4. S.E.K., A.P. and B. Cook designed experiments and wrote the manuscript.

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Correspondence to Boaz Cook or Ardem Patapoutian.

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The authors declare no competing financial interests.

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Kim, S., Coste, B., Chadha, A. et al. The role of Drosophila Piezo in mechanical nociception. Nature 483, 209–212 (2012). https://doi.org/10.1038/nature10801

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