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First published online 28 October 2008
doi: 10.1242/jcs.028423

Journal of Cell Science 121, 3693-3703 (2008)
Published by The Company of Biologists 2008
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Research Article

A dual role for caveolin-1 in the regulation of fibronectin matrix assembly by uPAR

Elizabeth Monaghan-Benson1, Cynthia Corley Mastick2 and Paula J. McKeown-Longo1,*

1 Center for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA
2 Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV 98557, USA

* Author for correspondence (e-mail: mckeowp{at}mail.amc.edu)

Accepted 1 August 2008

The relationship between the plasminogen activator system and integrin function is well documented but incompletely understood. The mechanism of uPAR-mediated signaling across the membrane and the molecular basis of uPAR-dependent activation of integrins remain important issues. The present study was undertaken to identify the molecular intermediates involved in the uPAR signaling pathway controlling {alpha}5β1-integrin activation and fibronectin polymerization. Disruption of lipid rafts with MβCD or depletion of caveolin-1 by siRNA led to the inhibition of uPAR-dependent integrin activation and stimulation of fibronectin polymerization in human dermal fibroblasts. The data indicate a dual role for caveolin-1 in the uPAR signaling pathway, leading to integrin activation. Caveolin-1 functions initially as a membrane adaptor or scaffold to mediate uPAR-dependent activation of Src and EGFR. Subsequently, in its phosphorylated form, caveolin-1 acts as an accessory molecule to direct trafficking of activated EGFR to focal adhesions. These studies provide a novel paradigm for the regulation of crosstalk among integrins, growth-factor receptors and uPAR.

Key words: Fibronectin, Extracellular matrix, uPAR, Integrin, Caveolin-1






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