Requirements for and consequences of Rac-dependent protrusion

Small GTPases of the Rac subfamily exert multiple functions, the most prominent of which includes stimulation of dynamic actin rearrangements at the cell periphery. Frequently, these actin reorganizations cause the protrusion of leaflets of plasma membrane, so-called lamellipodia, which remain anchored at flat surfaces during forward protrusion of migrating cells, or develop into ruffles when lifting up-and backwards. Ruffling membranes are also engaged in fluid and particle uptake during pino- and phagocytosis, respectively. In recent work, we sought to clarify the precise role of Rac GTPases in actin-based protrusion, using a gene disruption approach. Furthermore, we aimed at dissecting the function of its downstream target Arp2/3 complex employing its instantaneous inhibition during simultaneous Rac activation. These complementary approaches allow comparison of the consequences of Rac versus Arp2/3 complex loss of function at the cell periphery, and help to formulate a working hypothesis for how the actin network in lamellipodia is initiated and maintained. (C) 2014 Elsevier GmbH. All rights reserved.