Force-dependent Piezo1 recruitment to focal adhesions regulates adhesion maturation and turnover specifically in non-transformed cells

Piezo1 is a mechanosensitive Ca2+-permeable channel that has been implicated in a number of mechanosensing processes. It is diffusive on plasma membranes and activated by local membrane tension changes yet recent data suggest that Piezo1 activity is tightly coupled to the integrin-mediated actin cytoskeleton through a poorly understood mechanism. In our studies, we found that Piezo1 stably localizes to RGD matrix adhesions in normal but not in transformed cells. Piezo1 binding requires contractility and triggers local Ca2+ entry during adhesion formation and turnover. In transformed cells, Piezo1 level does not affect adhesion morphology; and there is no detectable Ca2+ influx around adhesions. Based upon these findings, we suggest that Piezo1 is a novel component of integrin-based adhesions in non-transformed cells and contributes to the distinct mechanosensing and Ca2+ signaling in normal vs transformed cells. Concentration of Piezo1 at adhesions is a key factor underlying Piezo1's physiological functions.