Views and Reviews Structure and Function of Profilin

Profilin is a ubiquitous actin monomer-binding protein, found in organisms from yeast to man. Biochemical studies indicate that profilin can regulate actin polymerization and have suggested some possible mechanisms. Early studies in Acanthamoebu, showing that profilin could reduce the rate and extent of actin polymerization, were consistent with a model in which free actin monomer is in equilibrium with both actin-profilin complexes and actin-actin complexes (i.e., filaments). Tobacman and Korn [ 19821 calculated that while profilin would not bind much actin monomer under physiological conditions, it could dramatically amplify any change in monomer concentration caused by other events in the cell. Electron microscopic studies of actin assembly in vitro revealed that profilin does more than simply sequester monomers [Pollard and Cooper, 19841. It also affects the two ends of the actin filament differently, retarding polymerization more at the “pointed” than at the “barbed” end (these names refer to the arrowhead appearance of actin filaments decorated with myosin heads). Profilin might accomplish this by binding to the surface of the actin monomer that makes contact with the pointed end of the filament, blocking interaction at that end. The other surface of the monomer would remain free to interact with the barbed end. A change in conformation in the monomer upon binding at the barbed end could then reduce its affinity for profilin. The functional consequence would be to increase the bias in actin polymerization toward the already favored barbed end of pre-existing filaments by more strongly inhibiting pointed-end polymerization and nucleation of new filaments.