Formins stimulate actin polymerization by promoting both filament nucleation and elongation. Because nucleation and elongation draw upon a common pool of actin monomers, the rate at which each reaction proceeds influences the other. This interdependent mechanism determines the number of filaments assembled over the course of a polymerization reaction, as well as their equilibrium lengths. In this study, we used kinetic modeling and in vitro polymerization reactions to dissect the contributions of filament nucleation and elongation to the process of formin-mediated actin assembly. We found that the rates of nucleation and elongation evolve over the course of a polymerization reaction. The period over which each process occurs is a key determinant of the total number of filaments that are assembled, as well as their average lengths at equilibrium. Inclusion of formin in polymerization reactions speeds filament nucleation, thus increasing the number and shortening the lengths of filaments that are assembled over the course of the reaction. Modulation of the elongation rate produces modest changes in the equilibrium lengths of formin-bound filaments. However, the dependence of filament length on the elongation rate is limited by the number of filament ends generated via formin’s nucleation activity. Sustained elongation of small numbers of formin-bound filaments, therefore, requires inhibition of nucleation via monomer sequestration and a low concentration of activated formin. Our results underscore the mechanistic advantage for keeping formin’s nucleation efficiency relatively low in cells, where unregulated actin assembly would produce deleterious effects on cytoskeletal dynamics. Under these conditions, differences in the elongation rates mediated by formin isoforms are most likely to impact the kinetics of actin assembly.

福尔马明通过促进细丝成核和伸长来刺激肌动蛋白聚合。因为成核和伸长利用肌动蛋白单体的共同池，每个反应进行的速率会影响另一个。这种相互依赖的机制决定了在聚合反应过程中组装的细丝数量，以及它们的平衡长度。在这项研究中，我们使用动力学模型和体外聚合反应来剖析细丝成核和伸长对福尔马明介导的肌动蛋白组装过程的贡献。我们发现成核和伸长率在聚合反应过程中不断变化。每个过程发生的时间是组装的长丝总数以及它们平衡时的平均长度的关键决定因素。在聚合反应中加入甲醛可加速长丝成核，从而增加在反应过程中组装的长丝的数量并缩短其长度。伸长率的调节会在形式结合的长丝的平衡长度上产生适度的变化。然而，细丝长度对伸长率的依赖性受到通过福尔明的成核活性产生的细丝末端数量的限制。因此，少量的福尔明结合细丝的持续伸长需要通过单体螯合和低浓度的活化福明来抑制成核。我们的研究结果强调了在细胞中保持formin 成核效率相对较低的机制优势，其中不受管制的肌动蛋白组装会对细胞骨架动力学产生有害影响。