Participation of caveolae in beta‐1 integrin‐mediated mechanotransduction

Abstract

Experimental evidence suggests that caveolae and integrins function as primary mechanosensors. We recently reported that shear stress-induced activation of β1 integrin resulted in Src-family kinase dependent phosphorylation of caveolin-1, a process that was necessary for recruitement of signaling molecules to β1 integrins sites and propagation of a mechanotransduction response. Based on these findings, we propose that caveolae and integrins are functionally linked in their mechanotransduction properties. Here, we exposed BAEC monolayers to shear stress then isolated caveolae vesicles form the plasma membrane. While little β1 integrin was present in caveolae derived from cells kept in static culture, shear stress induced β1 integrin transposition to the caveolae. Csk was detected in caveolae derived from non-shear cells and additional Csk was recruited to caveolae after shear. To evaluate the significance of shear-induced β1 integrin localization to caveolae, cells were pretreated with methyl-β-cyclodextrin (CD) to disrupt rafts/caveolae. CD attenuated integrin-dependent caveolin-1 phosphorylation, Csk association with β1 integrin and myosin light chain phosphorylation induced by shear. Taken together with our previous findings, the data supports the concept that β1 integrin-mediated mechanotransduction is mediated by raft/caveolae domains. Supported by NIH HL66301.