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First published online 24 June 2008
doi: 10.1242/jcs.014977

Journal of Cell Science 121, 2360-2371 (2008)
Published by The Company of Biologists 2008
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Research Article

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

Feng Shi and Jane Sottile*

Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, 211 Bailey Road, West Henrietta, NY 14586, USA

* Author for correspondence (e-mail: jane_sottile{at}urmc.rochester.edu)

Accepted 28 April 2008

β1 integrins are major cell surface receptors for fibronectin. Some integrins, including β1 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 β1 integrin endocytosis to fibronectin matrix turnover. First, we demonstrate that β1 integrins, including {alpha}5β1 play an important role in endocytosis and turnover of matrix fibronectin. Second, we show that caveolin-1 constitutively regulates endocytosis of {alpha}5β1 integrins, and that {alpha}5β1 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 β1 integrin and fibronectin endocytosis. Hence, caveolin-1-dependent β1 integrin and fibronectin endocytosis plays a critical role in fibronectin matrix turnover, and may contribute to abnormal ECM remodeling that occurs in fibrotic disorders.

Key words: Integrin, Extracellular matrix, Endocytosis, Caveolae, Fibrosis






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