Inactivation Kinetics and Mechanical Gating of Piezo1 Ion Channels Depend on Subdomains within the Cap.

Journal Article (Journal Article)

Piezo1 ion channels are activated by mechanical stimuli and mediate the sensing of blood flow. Although cryo-electron microscopy (cryo-EM) structures have revealed the overall architecture of Piezo1, the precise domains involved in activation and subsequent inactivation have remained elusive. Here, we perform a targeted chimeric screen between Piezo1 and the closely related isoform Piezo2 and use electrophysiology to characterize their inactivation kinetics during mechanical stimulation. We identify three small subdomains within the extracellular cap that individually can confer the distinct kinetics of inactivation of Piezo2 onto Piezo1. We further show by cysteine crosslinking that conformational flexibility of these subdomains is required for mechanical activation to occur and that electrostatic interactions functionally couple the cap to the extensive blades, which have been proposed to function as sensors of membrane curvature and tension. This study provides a demonstration of internal gating motions involved in mechanotransduction by Piezo1.

Full Text

Duke Authors

Cited Authors

  • Lewis, AH; Grandl, J

Published Date

  • January 21, 2020

Published In

Volume / Issue

  • 30 / 3

Start / End Page

  • 870 - 880.e2

PubMed ID

  • 31968259

Pubmed Central ID

  • 31968259

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2019.12.040

Language

  • eng

Conference Location

  • United States