Rho GTPases control polarity, protrusion, and adhesion during cell movement

Cell movement is essential during embryogenesis to establish tissue pattern s and to drive morphogenetic pathways and in the adult for tissue repair an d to direct cells to sites of infection. Animal cells move by crawling and the driving force is derived primarily from the coordinated assembly and di sassembly of actin filaments. The small GTPases, Rho, Rac, and Cdc42, regul ate the organization of actin filaments and we have analyzed their contribu tions to the movement of primary embryo fibroblasts in an in vitro wound he aling assay. Rac is essential for the protrusion of lamellipodia and for fo rward movement. Cdc42 is required to maintain cell polarity, which includes the localization of lamellipodial activity to the leading edge and the reo rientation of the Golgi apparatus in the direction of movement. Rho is requ ired to maintain cell adhesion during movement, but stress fibers and focal adhesions are not required. Finally, Ras regulates focal adhesion and stre ss fiber turnover and this is essential for cell movement. We conclude that the signal transduction pathways controlled by the four small GTPases, Rho , Rac, Cdc42, and Ras, cooperate to promote cell movement.