Caveolin-1-dependent β1 integrin endocytosis is a critical regulator of fibronectin turnover

beta 1 integrins are major cell surface receptors for fibronectin. Some integrins, including beta 1 integrins, are known to undergo constitutive endocytosis and recycling. Integrin endocytosis/recycling has been implicated in the regulation of cell migration. However, the mechanisms by which integrin endocytosis/recycling regulates cell migration, and other biological consequences of integrin trafficking are not completely understood. We previously showed that turnover of extracellular matrix (ECM) fibronectin occurs via receptor-mediated endocytosis. Here, we investigate the biological relevance of beta 1 integrin endocytosis to fibronectin matrix turnover. First, we demonstrate that beta 1 integrins, including alpha 5 beta 1 play an important role in endocytosis and turnover of matrix fibronectin. Second, we show that caveolin-1 constitutively regulates endocytosis of alpha 5 beta 1 integrins, and that alpha 5 beta 1 integrin endocytosis can occur in the absence of fibronectin and fibronectin matrix. We also show that downregulation of caveolin-1 expression by siRNA results in marked reduction of beta 1 integrin and fibronectin endocytosis. Hence, caveolin-1-dependent beta 1 integrin and fibronectin endocytosis plays a critical role in fibronectin matrix turnover, and may contribute to abnormal ECM remodeling that occurs in fibrotic disorders.