The mechanosensitive Piezo1 channel: structural features and molecular bases underlying its ion permeation and mechanotransduction

Abstract

The evolutionarily conserved Piezo family of proteins, including Piezo1 and Piezo2, encodes the long‐sought‐after mammalian mechanosensitive cation channels that play critical roles in various mechanotransduction processes such as touch, pain, proprioception, vascular development and blood pressure regulation. Mammalian Piezo proteins contain over 2500 amino acids with numerous predicted transmembrane segments, and do not bear sequence homology with any known class of ion channels. Thus, it is imperative, but challenging, to understand how they serve as effective mechanotransducers for converting mechanical force into electrochemical signals. Here, we review the recent major breakthroughs in determining the three‐bladed, propeller‐shaped structure of mouse Piezo1 using the state‐of‐the‐art cryo‐electron microscopy (cryo‐EM) and functionally dissecting out the molecular bases that define its ion permeation and mechanotransduction properties, which provide key insights into clarifying its oligomeric status and pore‐forming region. We also discuss the hypothesis that the complex Piezo proteins can be deduced into discrete mechanotransduction and ion‐conducting pore modules, which coordinate to fulfil their specialized function in mechanical sensing and transduction, ion permeation and selection.