Figure 3. Regulation of actin filament elongation in migrating neutrophils. Panel A illustrates the activity of the Arp2/3 complex in generating new filament ends. Two mechanisms have been proposed. In the top of the panel, Arp2/3 complex binds to the side of the filament with a characteristic 70° angle and nucleates the growth of a new filament with a free high-affinity end. In a separate model, the Arp2/3 complex binds to an existing high-affinity filament end and nucleates the growth of a new filament. Panel B illustrates the mechanism of uncapping, in which phosphoinositide lipids, illustrated with black head-groups within the phospholipid bilayer, stimulate the dissociation of an actin filament capping protein from the high-affinity end of the actin filament. This filament is then free to elongate. In panel C, we have tried to integrate these activities, as well as the activity of actin cross-linking proteins, to generate the structures found at the leading edge of a motile cell. In all panels, actin filaments are generated from the assembly of actin monomer in gray, the Arp2/3 complex is a collection of multi-component gray ovals, and the capping proteins are open circles.