THE RHO SMALL G-PROTEIN FAMILY RHO-GDI SYSTEM AS A TEMPORAL AND SPATIAL DETERMINANT FOR CYTOSKELETAL CONTROL

Recent extensive studies have clarified the functions of the small G p rotein superfamily, which consists of the Ras, Rho, Rab, Arf, Sari, an d Ran families (for reviews, Refs. 1 and 2). The Ras family regulates gene expression at least through the MAP kinase cascade; the Rho famil y mainly regulates reorganization of the actin cytoskeleton; the Rab, Arf, and Sari families regulate intracellular vesicle trafficking; and the Ran family regulates nuclear transport. Of these cellular functio ns, reorganization of the actin cytoskeleton, seen in the formation of filopodia, lamellipodia, and ruffles during cell motility, dynamicall y occurs at specific sites of cells. To regulate this type of dynamic cellular functions, temporal and spatial determination mechanisms of s ignal transduction would be important. Like other G proteins, small G proteins cycle between the GDP-bound inactive and GTP-bound active for ms (1,2). They receive upstream signals through their regulators and t ransduce signals to downstream targets while they stay in the GTP-boun d form. Thus, G;proteins serve as timers. There are at least three typ es of regulators for small G proteins: GDP/GTP exchange protein (GEP) which stimulates conversion from the GDP-bound form to the GTP-bound f orm; GDP dissociation inhibitor (GDI) which inhibits this reaction; an d GTPase activating protein (GAP) which stimulates conversion from the GTP-bound form to the GDP-bound form. Of these regulators, GDI has th us far been found for the Rho and Rab families. We have recently found that the Rho family-Rho GDI system plays an important role in spatial determination in the actin cytoskeletal control (3-6). We briefly des cribe here this function of the Rho family-Rho GDI system. (C) 1998 Ac ademic Press.