Recent quantitative studies of actin filament turnover during cell locomotion.

Abstract

Cell locomotion depends on polymerization and depolymerization of filamentous actin. Net polymerization at the cell front occurs fast enough to fill the extending lamellipod, and since total F-actin is essentially constant over time, depolymerization must equal polymerization. Indeed, the fastest moving cell types have the highest rates of depolymerization. Accounting for the high rate of depolymerization raises several problems. One is that net depolymerization requires the concentration of G-actin to be low (below the critical concentration), but rapid polymerization (occurring < 1 micron away) requires the concentration of G-actin to be high (well above the critical concentration). This may be accomplished by spatial compartmentalization of factors that favor polymerization or depolymerization, and/or by proteins that bind G-actin and prevent spontaneous polymerization while allowing barbed-end elongation. A second problem is that depolymerization proceeds faster than would seem possible from studies of F-actin in vitro (as calculated from number and lengths of filaments present and in vitro rate constants). Rapid depolymerization may be accomplished by filament cutters or by cytoplasmic components (as yet undiscovered) that increase the rate of depolymerization.