Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 358, Issue 2, Pages 626-631Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2007.04.179
Keywords
Caveolae; integrins; mechanotransduction; shear stress; lipid rafts
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Funding
- NHLBI NIH HHS [R01 HL066301, HL66301, R01 HL066301-06] Funding Source: Medline
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We previously reported that caveolin-1 is a key component in a beta 1 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 beta 1 integrin was detected in caveolae derived from cells kept in static culture, shear stress induced beta 1 integrin transposition to the caveolae. To evaluate the significance of shear-induced beta 1 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 beta 1 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 beta 1 integrin-mediated mechanotransduction is mediated by caveolae domains. (C) 2007 Elsevier Inc. All rights reserved.
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