Shear stress-induced cytoskeletal rearrangement involves caveolae-mediated mechanotransduction

Shear stress alters vascular endothelial cell morphology through remodeling of the actin cytoskeleton. The rapid cytoskeletal responses of bovine aortic cell (BAEC) monolayers to shear (10-12 dynes/cm²) were measured in terms of accumulation of di-phosphorylated myosin light chain (MLC). This effect was attenuated by pretreatment with filipin, a cholesterol-sequestering agent known to disrupt the structure of lipid rafts and unique membrane microdomains called caveolae. RhoA, the small GTPase known to regulate actin stress fiber formation, co-localized with caveolin-1, the structural protein of caveolae. The existence of a potential consensus-binding motif for caveolin-1 near the catalytic domain of RhoA suggests that caveolin-1 may regulate RhoA activity. To further examine the relationship between caveolin and RhoA, luminal/apical cell membranes were purified from shear-conditioned BAEC monolayers. Analysis of these fractions showed that shear stress stimulated translocation of RhoA to the luminal plasma membrane, an event that correlated with RhoA activation in the whole cell. Current studies are underway to determine the roles of caveolin-1 and RhoA in the mechanotransduction processes that lead to the morphological restructuring of endothelial cells in response to shear stress.