A model for phospho-caveolin-1-driven turnover of focal adhesions.
The regulation of Focal Adhesion (FA) dynamics is a key aspect of cellular motility. FAs concentrate integrins and associated cytoskeletal elements as well as a large number of regulatory proteins, including adapters, kinases and small GTPases of the Rho Family. We have recently shown that activated Rac1 can localize to FAs and can initiate the accumulation of the adapter protein Caveolin1 (Cav1) at FAs. As reported by several groups including ours, this translocation requires Cav1 phosphorylation at Tyr14, presumably by Src. Here we provide additional data regarding this process and briefly review recent literature. Finally, we incorporated the different pieces of available information into a mechanistic model. This model proposes that local Rac1 activation initiates a series of events that involve endosomal traffic of Cav1 and Src, targeting these proteins to or near FAs. Next, within specific membrane domains, Src can mediate the phosphorylation of Cav1 at Tyr 14, which is important for the stable FA localization of Cav1. Finally, dephosphorylation of Cav1 may represent a key step required for internalization, FA turnover and cell motility.
Department of Molecular Cell Biology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. m.nethe@sanquin.nl
Micha
M
Nethe
Peter L
PL
Hordijk
D051242:Caveolin 1 / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D022001:Focal Adhesions / Q000378:metabolism* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism* / Q000502:physiology
D051242:Caveolin 1; D016023:Integrins; D019061:src-Family Kinases; D020830:rac1 GTP-Binding Protein