Journal Article

A protein interaction mechanism for suppressing the mechanosensitive Piezo channels

Xiao, Bailong, Chi, Shaopeng, Zhao, Qiancheng, Zhang, Tingxin, Jiang, Fan

2017

Overview

Piezo proteins are bona fide mammalian mechanotransduction channels for various cell types including endothelial cells. The mouse Piezo1 of 2547 residues forms a three-bladed, propeller-like homo-trimer comprising a central pore-module and three propeller-structures that might serve as mechanotransduction-modules. However, the mechanogating and regulation of Piezo channels remain unclear. Here we identify the sarcoplasmic /endoplasmic-reticulum Ca 2+ ATPase (SERCA), including the widely expressed SERCA2, as Piezo interacting proteins. SERCA2 strategically suppresses Piezo1 via acting on a 14-residue-constituted intracellular linker connecting the pore-module and mechanotransduction-module. Mutating the linker impairs mechanogating and SERCA2-mediated modulation of Piezo1. Furthermore, the synthetic linker-peptide disrupts the modulatory effects of SERCA2, demonstrating the key role of the linker in mechanogating and regulation. Importantly, the SERCA2-mediated regulation affects Piezo1-dependent migration of endothelial cells. Collectively, we identify SERCA-mediated regulation of Piezos and the functional significance of the linker, providing important insights into the mechanogating and regulation mechanisms of Piezo channels. Mechanosensitive Piezo channels are important for a wide range of mechanotransduction processes. Here the authors show that Piezos interact with sarcoplasmic /endoplasmic-reticulum Ca 2+ ATPases (SERCA) and give mechanistic insights into mechanogating and SERCA2-mediated regulation of Piezo1.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/57/2283 / 631/80/86/2372 / Adenosine triphosphatase / Blood / Ca2+-transporting ATPase / Calcium / Cell Movement - physiology / Channels / Endothelial cells / Gene Knockdown Techniques / HEK293 Cells / Human Umbilical Vein Endothelial Cells / Humanities and Social Sciences / Humans / Ion Channel Gating - physiology / Ion Channels - chemistry / Ion Channels - genetics / Ion Channels - metabolism / Life sciences / Mechanotransduction / Mechanotransduction, Cellular - physiology / Models, Molecular / multidisciplinary / Peptides - chemical synthesis / Peptides - metabolism / Proteins / RNA, Small Interfering - metabolism / Sarcoplasmic Reticulum Calcium-Transporting ATPases - chemistry / Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism / Science / Science (multidisciplinary)