Regulation of PIEZO1 channels by lipids and the structural components of extracellular matrix/cell cytoskeleton

Abstract PIEZO1 is a mechanosensitive channel widely presented in eukaryotic organisms. Although the PIEZO family was discovered in 2010, main questions related to the molecular structure as well as to specific activation mechanisms and regulating pathways remain open. Two hypotheses of PIEZO1 gating were formulated: the first, as a dominant hypothesis, through the plasma membrane (force‐from‐lipids) and the second, via the participation of the cytoskeleton and the components of the extracellular matrix (ECM) (force‐from‐filaments). Many researchers provide convincing evidence for both hypotheses. It was demonstrated that PIEZO1 has a propeller‐like shape forming a membrane curvature within the lipid bilayer. That suggests the participation of lipids in channel modulation, and many studies demonstrate the critical role of lipids and compounds that modify the lipid bilayer in the regulation of PIEZO1 properties. At the same time, the components of ECM and cortical cytoskeleton can be affected by the membrane curvature and thus have an impact on PIEZO1 properties. In living cells, PIEZO1 properties are reported to be critically dependent on channel microenvironment that is on combinatorial influence of plasma membrane, cytoskeleton and ECM. Thus, it is necessary to understand which factors can affect PIEZO1 and consider them when interpreting the role of PIEZO1 in various physiological processes. This review summarizes the current knowledge about regulation of Piezo1 by lipids and the components of ECM and cytoskeleton.