Formins initiate actin filaments at various places such as filopodia, focal adhesions, and the cytokinetic ring. The authors show that when formin is alone on barbed ends, it slows filament dynamics by binding to and falling off the barbed ends. But when another actin-binding protein, profilin, is added, formin becomes a processive motor for rapid actin elongation.
The profilin/formin combination speeds polymerization two ways. First, it increases by 15-fold the on-rate of actin to barbed ends. “Electrostatic or hydrodynamic properties of formin,” suggests Carlier, “may allow profilin–actin to associate much faster at short distances than is [possible when] limited by diffusion.” This is a much faster rate than that of Arp2/3. The disparate on-rate constants thus allow for different actin velocities at the same actin monomer concentration.
Formin's second ability is to hasten ATP hydrolysis by actin, which is the rate-limiting step of filament growth at high actin–profilin levels. Enhanced hydrolysis may result from structural changes to the ATP-binding site, which should be revealed by structural studies of actin–formin–profilin.