title: Participation of caveolae in beta1 integrin-mediated mechanotransduction.
abstract: We previously reported that caveolin-1 is a key component in a beta1 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 beta1 integrin was detected in caveolae derived from cells kept in static culture, shear stress induced beta1 integrin transposition to the caveolae. To evaluate the significance of shear-induced beta1 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 beta1 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 beta1 integrin-mediated mechanotransduction is mediated by caveolae domains.
authors.affiliation: Cardiovascular Research Center and Department of Anatomy & Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Radel
authors.forename: Maryellen
authors.initials: M
authors.lastname: Carlile-Klusacek
authors.forename: Victor
authors.initials: V
authors.lastname: Rizzo
mesh_terms: D000818:Animals; D002417:Cattle; D021941:Caveolae / Q000502:physiology*; D051242:Caveolin 1 / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D019012:Integrin beta1 / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*
chemical_list: D051242:Caveolin 1; D019012:Integrin beta1