Participation of caveolae in β1 integrin-mediated mechanotransduction

We previously reported that caveolin-1 is a key component in a β1 integrin-dependent mechanotransduction pathway suggesting that caveolae organelles 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 detected in caveolae derived from cells kept in static culture, shear stress induced β1 integrin transposition to the caveolae. To evaluate the significance of shear-induced β1 integrin localization to caveolae, cells were pretreated with cholesterol sequestering compounds or caveolin-1 siRNA to disrupt caveolae structural domains. Cholesterol depletion attenuated integrin-dependent caveolin-1 phosphorylation, Src activation and Csk association with β1 integrin. Reduction of both caveolin-1 protein and membrane cholesterol inhibited downstream shear-induced, integrin-dependent phosphorylation of myosin light chain. Taken together with our previous findings, the data supports the concept that β1 integrin-mediated mechanotransduction is mediated by caveolae domains.