The role of Drosophila Piezo in mechanical nociception (original) (raw)

Nature volume 483, pages 209–212 (2012)Cite this article

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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 (Dm_piezo_; also known as CG8486). Dm_piezo_ expression in human cells induces mechanically activated currents, similar to its mammalian counterparts[11](/articles/nature10801#ref-CR11 "Coste, B. et al. Piezo proteins are pore-forming subunits of mechanically activated channels. Nature 483, http://dx.doi.org/10.1038/nature10812

             (this issue)"). Behavioural responses to noxious mechanical stimuli were severely reduced in Dm_piezo_ knockout larvae, whereas responses to another noxious stimulus or touch were not affected. Knocking down Dm_piezo_ 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 Dm_piezo_ in these same neurons rescued the phenotype of the constitutive Dm_piezo_ knockout larvae. Accordingly, electrophysiological recordings from _ppk_\-positive neurons revealed a Dm_piezo_\-dependent, mechanically activated current. Finally, we found that Dm_piezo_ 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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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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Authors and Affiliations

  1. Department of Cell Biology, Dorris Neuroscience Center, The Scripps Research Institute (TSRI), La Jolla, 92037, California, USA
    Sung Eun Kim, Bertrand Coste, Abhishek Chadha, Boaz Cook & Ardem Patapoutian
  2. Genomic Institute of the Novartis Research Foundation (GNF), San Diego, 92121, California, USA
    Ardem Patapoutian

Authors

  1. Sung Eun Kim
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  2. Bertrand Coste
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  3. Abhishek Chadha
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  4. Boaz Cook
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  5. Ardem Patapoutian
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Contributions

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.

Corresponding authors

Correspondence toBoaz 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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Editorial Summary

Piezo ion channel feels the force

Many tissues are able to detect and respond to mechanical forces, and this mechanical sensitivity has been implicated in many biological processes and diseases, including touch, pain, deafness and hypertension. The conversion of mechanical force into biological signals, or 'mechanotransduction', is thought to involve specialized cation channels. In a pair of papers, Ardem Patapoutian and colleagues establish that the large transmembrane proteins of the 'Piezo' family — conserved from animals to plants and protozoa — are among the long-sought-after mechanically activated ion channels. Coste et al. show that the Drosophila melanogaster Piezo protein induces mechanically activated cationic currents in human embryonic kidney cells, establishing functional conservation. Comparison of the mechanically activated currents induced by mouse and fly Piezos reveals ion-channel activities with unique pore properties, suggesting that Piezos are bona fide ion channels. Kim et al. show that D. melanogaster Piezo is essential for sensing mechanical pain in fruitflies, giving the first demonstration that Piezos are physiologically relevant mechanosensors in vivo.

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