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Journal Articles eLife Year : 2015

Chemical activation of the mechanotransduction channel Piezo1

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Ruhma Syeda
  • Function : Author
Jie Xu
  • Function : Author
Adrienne Dubin
  • Function : Author
Jayanti Mathur
  • Function : Author
Truc Huynh
  • Function : Author
Jason Matzen
  • Function : Author
Jianmin Lao
  • Function : Author
David Tully
  • Function : Author
Ingo Engels
  • Function : Author
H Michael Petrassi
  • Function : Author
Andrew Schumacher
  • Function : Author
Mauricio Montal
  • Function : Author
Michael Bandell
  • Function : Author
Ardem Patapoutian
  • Function : Author

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. In this study, 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.

Dates and versions

hal-03464372 , version 1 (03-12-2021)

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Ruhma Syeda, Jie Xu, Adrienne Dubin, Bertrand Coste, Jayanti Mathur, et al.. Chemical activation of the mechanotransduction channel Piezo1. eLife, 2015, 4, ⟨10.7554/eLife.07369⟩. ⟨hal-03464372⟩
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