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Published online May 21, 2007
doi:10.1083/jcb.200701006
The Journal of Cell Biology, Vol. 177, No. 4, 683-694
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Grande-García et al.
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Article

 Caveolin-1 regulates cell polarization and directional migration through Src kinase and Rho GTPases

Araceli Grande-García1, Asier Echarri1, Johan de Rooij2, Nazilla B. Alderson1, Clare M. Waterman-Storer2, José M. Valdivielso1, and Miguel A. del Pozo1

1 Integrin Signaling Laboratory, Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain
2 Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037

Correspondence to Miguel A. del Pozo: madelpozo{at}cnic.es

Development, angiogenesis, wound healing, and metastasis all involve the movement of cells in response to changes in the extracellular environment. To determine whether caveolin-1 plays a role in cell migration, we have used fibroblasts from knockout mice. Caveolin-1–deficient cells lose normal cell polarity, exhibit impaired wound healing, and have decreased Rho and increased Rac and Cdc42 GTPase activities. Directional persistency of migration is lost, and the cells show an impaired response to external directional stimuli. Both Src inactivation and p190RhoGAP knockdown restore the wild-type phenotype to caveolin-1–deficient cells, suggesting that caveolin-1 stimulates normal Rho GTP loading through inactivation of the Src–p190RhoGAP pathway. These findings highlight the importance of caveolin-1 in the establishment of cell polarity during directional migration through coordination of the signaling of Src kinase and Rho GTPases.

J. de Rooij's present address is Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.

J.M. Valdivielso's present address is Hospital Universitario Arnau de Vilanova, Universidad de Lleida, 25198 Lleida, Spain.

Abbreviations used in this paper: Csk, C-terminal Src kinase; EF, elliptical factor; FA, focal adhesion; Fn, fibronectin; ID, index of directionality; MEF, mouse embryonic fibroblast; MTOC, microtubule organizing center; shRNA, short hairpin RNA; WT, wild-type.


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