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Chemical activation of the mechanotransduction channel Piezo1

Bandell, Michael and Xu, Jie and Mathur, Jayanti and Huynh, Truc and Matzen, Jason and Lao, Jianmin and Tully, David and Petrassi, Hank and Schumacher, Andrew and montal, Mauricio and syeda, Ruhma and Dubin, Adrienne and Coste, Bertrand and Patapoutian, Ardem (2015) Chemical activation of the mechanotransduction channel Piezo1. eLife, 4 (MAY). ISSN 2050084X

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.

Item Type: Article
Date Deposited: 10 Mar 2018 00:45
Last Modified: 25 Jan 2019 00:45
URI: https://oak.novartis.com/id/eprint/24813

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