Rho GTPases control actin reorganization and many other cellular functions. Guanine nucleotide-exchange factors (GEFs) activate Rho GTPases by promoting their exchange of GDP for GTP. Trio is a unique Rho GEF, because it has separate GEF domains, GEFD1 and GEFD2, that control the GTPases RhoG/Rac1 and RhoA, respectively, Dbl-homology (DH) domains that are common to GEFs catalyse nucleotide exchange, and pleckstrin-homology (PH) domains localize Rho GEFs near their downstream targets, Here we show that Trio GEFD1 interacts through its PH domain with the actin-filament-crosslinking protein filamin, and localizes with endogenous filamin in HeLa cells. Trio GEFD1 induces actin-based ruffling in filamin-expressing, but not filamin-deficient, cells and in cells transfected with a filamin construct that lacks the Trio-binding domain. In addition, Trio GEFD1 exchange activity is not affected by filamin binding. Our results indicate that filamin, as a molecular target of Trio, may be a scaffold for the spatial organization of Rho-GTPase-mediated signalling pathways.
The Rac1-and RhoG-specific GEF domain of Trio targets filamin to remodel cytoskeletal actin
Bellanger, J. M.; Astier, C.; Sardet, C.; Ohta, Y.; Stossel, T. P.; Debant, A.
Nature Cell Biology
2000-12 / vol 2 / pages 888-892
phosphatase; gtpases; kinase; binding protein; rac; exchange factor domains; arp2/3 complex; cell-adhesion; pleckstrin homology domains; protein-interaction domain