Caveolin-1 regulates cell polarization and directional migration through Src kinase and Rho GTPases.
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.
Grande-García
Araceli
A
Integrin Signaling Laboratory, Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
Echarri
Asier
A
de Rooij
Johan
J
Alderson
Nazilla B
NB
Waterman-Storer
Clare M
CM
Valdivielso
José M
JM
del Pozo
Miguel A
MA
D000818:Animals; D051242:Caveolin 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D015398:Signal Transduction / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology*; D019061:src-Family Kinases / Q000502:physiology*
D051242:Caveolin 1; D019061:src-Family Kinases; D020741:rho GTP-Binding Proteins