Nature Cell Biology 4, 232 - 239 (2002)
Published online: 25 February 2002; | doi:10.1038/ncb759
Integrins regulate GTP-Rac localized effector interactions through dissociation of Rho-GDI
Miguel Angel Del Pozo 1, 2, William B. Kiosses 1, 2, Nazilla B. Alderson 1, 2, Nahum Meller 1, 2, Klaus M. Hahn 2 & Martin Alexander Schwartz 1, 2
1 Division of Vascular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA
2 Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA
Correspondence should be addressed to Miguel Angel Del Pozo mdelpozo@scripps.edu or Martin Alexander Schwartz schwartz@scripps.edu
The proper function of Rho GTPases requires precise spatial and temporal regulation of effector interactions. Integrin-mediated cell adhesion modulates the interaction of GTP-Rac with its effectors by controlling GTP-Rac membrane targeting. Here, we show that the translocation of GTP-Rac to membranes is independent of effector interactions, but instead requires the polybasic sequence near the carboxyl terminus. Cdc42 also requires integrin-mediated adhesion for translocation to membranes. A recently developed fluorescence resonance energy transfer (FRET)-based assay yields the surprising result that, despite its uniform distribution, the interaction of activated V12-Rac with a soluble, cytoplasmic effector domain is enhanced at specific regions near cell edges and is induced locally by integrin stimulation. This enhancement requires Rac membrane targeting. We show that Rho-GDI, which associates with cytoplasmic GTP-Rac, blocks effector binding. Release of Rho-GDI after membrane translocation allows Rac to bind to effectors. Thus, Rho-GDI confers spatially restricted regulation of Rac−effector interactions.
