Regulation of actin filament network formation through Arp2/3 complex: Activation by a diverse array of proteins

Actin filament assembly and turnover drive many forms of cellular motility, particularly extension of the leading edge of locomoting cells and rocketi ng of pathogenic microorganisms through host cell cytoplasm. De novo nuclea tion of actin filaments appears to be required for these movements. A compl ex of seven proteins called Arp2/3 complex is the best characterized cellul ar initiator of actin filament nucleation. Arp2/3 complex is intrinsically inactive, relying on nucleation promoting factors for activation. WASp/Scar family proteins are prominent cellular nucleation promoting factors. They bring together an actin monomer and Arp2/3 complex in solution or on the si de of an existing actin filament to initiate a new filament that grows in t he barbed end direction. WASp and N-WASP are intrinsically autoinhibited, a nd their activity is regulated by Rho-family GTPases such as Cdc42, membran e polyphosphoinositides, WIP/verprolin, and SH3 domain proteins. These inte ractions provide a final common pathway for many signaling inputs to regula te actin polymerization. Microorganisms either activate Arp2/3 complex dire ctly or usurp N-WASP to initiate actin polymerization.