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Chemical activation of the mechanotransduction channel Piezo1

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 s...

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Autores principales: Syeda, Ruhma, Xu, Jie, Dubin, Adrienne E, Coste, Bertrand, Mathur, Jayanti, Huynh, Truc, Matzen, Jason, Lao, Jianmin, Tully, David C, Engels, Ingo H, Petrassi, H Michael, Schumacher, Andrew M, Montal, Mauricio, Bandell, Michael, Patapoutian, Ardem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456433/
https://www.ncbi.nlm.nih.gov/pubmed/26001275
http://dx.doi.org/10.7554/eLife.07369
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author Syeda, Ruhma
Xu, Jie
Dubin, Adrienne E
Coste, Bertrand
Mathur, Jayanti
Huynh, Truc
Matzen, Jason
Lao, Jianmin
Tully, David C
Engels, Ingo H
Petrassi, H Michael
Schumacher, Andrew M
Montal, Mauricio
Bandell, Michael
Patapoutian, Ardem
author_facet Syeda, Ruhma
Xu, Jie
Dubin, Adrienne E
Coste, Bertrand
Mathur, Jayanti
Huynh, Truc
Matzen, Jason
Lao, Jianmin
Tully, David C
Engels, Ingo H
Petrassi, H Michael
Schumacher, Andrew M
Montal, Mauricio
Bandell, Michael
Patapoutian, Ardem
author_sort Syeda, Ruhma
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.07369.001
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spelling pubmed-44564332015-06-05 Chemical activation of the mechanotransduction channel Piezo1 Syeda, Ruhma Xu, Jie Dubin, Adrienne E Coste, Bertrand Mathur, Jayanti Huynh, Truc Matzen, Jason Lao, Jianmin Tully, David C Engels, Ingo H Petrassi, H Michael Schumacher, Andrew M Montal, Mauricio Bandell, Michael Patapoutian, Ardem eLife Biophysics and Structural Biology 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. DOI: http://dx.doi.org/10.7554/eLife.07369.001 eLife Sciences Publications, Ltd 2015-05-22 /pmc/articles/PMC4456433/ /pubmed/26001275 http://dx.doi.org/10.7554/eLife.07369 Text en © 2015, Syeda et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biophysics and Structural Biology
Syeda, Ruhma
Xu, Jie
Dubin, Adrienne E
Coste, Bertrand
Mathur, Jayanti
Huynh, Truc
Matzen, Jason
Lao, Jianmin
Tully, David C
Engels, Ingo H
Petrassi, H Michael
Schumacher, Andrew M
Montal, Mauricio
Bandell, Michael
Patapoutian, Ardem
Chemical activation of the mechanotransduction channel Piezo1
title Chemical activation of the mechanotransduction channel Piezo1
title_full Chemical activation of the mechanotransduction channel Piezo1
title_fullStr Chemical activation of the mechanotransduction channel Piezo1
title_full_unstemmed Chemical activation of the mechanotransduction channel Piezo1
title_short Chemical activation of the mechanotransduction channel Piezo1
title_sort chemical activation of the mechanotransduction channel piezo1
topic Biophysics and Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456433/
https://www.ncbi.nlm.nih.gov/pubmed/26001275
http://dx.doi.org/10.7554/eLife.07369
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