Chemical activation of the mechanotransduction channel Piezo1

Ruhma Syeda, Jie Xu, Adrienne E. Dubin, Bertrand Coste, Jayanti Mathur, Truc Huynh, Jason Matzen, Jianmin Lao, David C. Tully, Ingo H. Engels, H. Michael Petrassi, Andrew M. Schumacher, Mauricio Montal, Michael Bandell, Ardem Patapoutian

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

Piezo ion channels are activated by various types of mechanical stimuli and function as biological pressure sensors in both vertebrates and invertebrates. To date mechanical stimuli are the only means to activate Piezo ion channels and whether other modes of activation exist is not known. Here, we screened ~3.25 million compounds using a cell-based fluorescence assay and identified a synthetic small molecule we termed Yoda1 that acts as an agonist for both human and mouse Piezo1. Functional studies in cells revealed that Yoda1 affects the sensitivity and the inactivation kinetics of mechanically induced responses. Characterization of Yoda1 in artificial droplet lipid bilayers showed that Yoda1 activates purified Piezo1 channels in the absence of other cellular components. Our studies demonstrate that Piezo1 is amenable to chemical activation, and raise the possibility that endogenous Piezo1 agonists might exist. Yoda1 will serve as a key tool compound to study Piezo1 regulation and function.

Original languageEnglish (US)
Article numbere07369
JournaleLife
Volume4
Issue numberMAY
DOIs
StatePublished - May 22 2015

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Syeda, R., Xu, J., Dubin, A. E., Coste, B., Mathur, J., Huynh, T., Matzen, J., Lao, J., Tully, D. C., Engels, I. H., Michael Petrassi, H., Schumacher, A. M., Montal, M., Bandell, M., & Patapoutian, A. (2015). Chemical activation of the mechanotransduction channel Piezo1. eLife, 4(MAY), [e07369]. https://doi.org/10.7554/eLife.07369