Molecular mechanisms controlling actin filament dynamics in nonmuscle cells

We review how motile cells regulate actin filament assembly at their leadin g edge. Activation of cell surface receptors generates signals (including a ctivated Rho family GTPases) that converge on integrating proteins of the W ASp family (WASp, N-WASP, and Scar/WAVE). WASP family proteins stimulate Ar p2/3 complex to nucleate actin filaments, which grow at a fixed 70 degrees angle from the side of pre-existing actin filaments. These filaments push t he membrane forward as they grow at their barbed ends. Arp2/3 complex is in corporated into the network, and new filaments are capped rapidly, so that activated Arp2/3 complex must be supplied continuously to keep the network growing. Hydrolysis of ATP bound to polymerized actin followed by phosphate dissociation marks older filaments for depolymerization by ADF/cofilins. P rofilin catalyzes exchange of ADP for ATP, recycling actin back to a pool o f unpolymerized monomers bound to profilin and thymosin-beta 4 that is pois ed for rapid elongation of new barbed ends.