The role of Drosophila Piezo in mechanical nociception

Transduction of mechanical stimuli by receptor neurons is essential for senses such as hearing, touch, and pain(1–4). Ion channels play a role in neuronal mechanotransduction in invertebrates(1); however, functional conservation of these ion channels in mammalian mechanotransduction is not observed. For example, NOMPC, a TRP ion channel, acts as a mechanotransducer in Drosophila melanogaster(5) and Caenorhabditis elegans(6,7); however, it has no orthologues in mammals. DEG/ENaC family members are mechanotransducers in C. elegans(8) and potentially in D. melanogaster(9); however, a direct role of its mammalian homologues in sensing mechanical force is not shown. Recently, Piezo1 and Piezo2 were identified as components of mechanically activated (MA) channels in mammals(10). Piezos represent an evolutionary conserved family of transmembrane proteins. It is unknown whether Piezos 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 (dpiezo). dpiezo expression in human cells induces mechanically activated currents, similar to its mammalian counterparts [Coste et al., accompanying paper(11)]. Behavioral responses to noxious mechanical stimuli were severely reduced in dpiezo knockout larvae, while responses to another noxious stimulus or touch were not affected. Knocking down dpiezo 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 dpiezo in these same neurons rescued the phenotype of the constitutive dpiezo knockout larvae. Accordingly, electrophysiological recordings from ppk-positive neurons revealed a dpiezo dependent, mechanically-activated current. Finally, we found that dpiezo 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 physiological relevance of Piezo family in mechanotransduction in vivo, supporting a role of Piezo proteins in mechanosensory nociception.