Dendritic actin networks develop from a first actin filament through branching by the Arp2/3 complex. At the surface of endosomes, the WASH complex activates the Arp2/3 complex and interacts with the capping protein for unclear reasons. Here, we show that the WASH complex interacts with dynactin and uncaps it through its FAM21 subunit. In vitro, the uncapped Arp1/11 minifilament elongates an actin filament, which then primes the WASH-induced Arp2/3 branching reaction. In dynactin-depleted cells or in cells where the WASH complex is reconstituted with a FAM21 mutant that cannot uncap dynactin, formation of branched actin at the endosomal surface is impaired. Our results reveal the importance of the WASH complex in coordinating two complexes containing actin-related proteins.

树突状肌动蛋白网络从第一肌动蛋白丝通过 Arp2/3 复合物分支发展而来。在内体表面，WASH 复合物激活 Arp2/3 复合物并与加帽蛋白相互作用，原因尚不清楚。在这里，我们展示了 WASH 复合物与 dynactin 相互作用并通过其 FAM21 亚基将其脱帽。在体外，未加帽的 Arp1/11 微丝会拉长肌动蛋白丝，然后引发 WASH 诱导的 Arp2/3 分支反应。在动力蛋白耗尽的细胞中或在用不能解开动力蛋白帽的 FAM21 突变体重建 WASH 复合物的细胞中，在内体表面分支肌动蛋白的形成受到损害。我们的结果揭示了 WASH 复合物在协调两个含有肌动蛋白相关蛋白的复合物中的重要性。