RRC ID 21872
Author Kim SE, Coste B, Chadha A, Cook B, Patapoutian A.
Title The role of Drosophila Piezo in mechanical nociception.
Journal Nature
Abstract Transduction of mechanical stimuli by receptor cells is essential for senses such as hearing, touch and pain. Ion channels have a role in neuronal mechanotransduction in invertebrates; 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 melanogaster and Caenorhabditis elegans; however, it has no orthologues in mammals. Degenerin/epithelial sodium channel (DEG/ENaC) family members are mechanotransducers in C. elegans and potentially in D. melanogaster; 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 mammals. 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 counterparts. 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.
Volume 483(7388)
Pages 209-12
Published 2012-2-19
DOI 10.1038/nature10801
PII nature10801
PMID 22343891
PMC PMC3297676
MeSH Animals Conserved Sequence Drosophila Proteins / chemistry Drosophila Proteins / deficiency Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development Drosophila melanogaster / physiology* Gene Deletion HEK293 Cells Humans Ion Channels / chemistry Ion Channels / deficiency Ion Channels / genetics Ion Channels / metabolism* Larva / genetics Larva / metabolism Mechanoreceptors / metabolism Mechanotransduction, Cellular / genetics Mechanotransduction, Cellular / physiology* Nociception / physiology* Sensory Receptor Cells / metabolism* Sodium Channels / deficiency Sodium Channels / genetics Sodium Channels / metabolism
IF 42.779
Times Cited 215
Drosophila 8486R-3