Profilin Interaction with Actin Filament Barbed End Controls Dynamic Instability, Capping, Branching, and Motility

Cell motility and actin homeostasis depend on the control of polarized growth of actin filaments. Profilin, an abundant regulator of actin dynamics, supports filament assembly at barbed ends by binding G-actin. Here, we demonstrate how, by binding and destabilizing filament barbed ends at physiological concentrations, profilin also controls motility, cell migration, and actin homeostasis. Profilin enhances filament length fluctuations. Profilin competes with Capping Protein at barbed ends, which generates a lower amount of profilin-actin than expected if barbed ends were tightly capped. Profilin competes with barbed end polymerases, such as formins and VopF, and inhibits filament branching by WASP-Arp2/3 complex by competition for filament barbed ends, accounting for its as-yet-unknown effects on motility and metastatic cell migration observed in this concentration range. In conclusion, profilin is a major coordinator of polarized growth of actin filaments, controlled by competition between barbed end cappers, trackers, destabilizers, and filament branching machineries. [Display omitted] •The binding of profilin to barbed ends accounts for its effects on cell migration•Profilin enhances length fluctuations of actin filaments by destabilizing barbed ends•Profilin competes with capping protein at filament barbed ends•Profilin competes with polymerases and filament branching machineries at barbed ends Pernier et al. demonstrate how the binding of profilin to actin filament barbed ends affects actin homeostasis during cell migration. Profilin competes with and coordinates the function of barbed end regulators including Capping Protein, polymerases such as formin or VASP, and WASP-Arp2/3 filament branching machineries.