The dynamin GTPase is known to bundle actin filaments, but the underlying molecular mechanism and physiological relevance remain unclear. Our genetic analyses revealed a function of dynamin in propelling invasive membrane protrusions during myoblast fusion in vivo. Using biochemistry, total internal reflection fluorescence microscopy, electron microscopy and cryo-electron tomography, we show that dynamin bundles actin while forming a helical structure. At its full capacity, each dynamin helix captures 12–16 actin filaments on the outer rim of the helix. GTP hydrolysis by dynamin triggers disassembly of fully assembled dynamin helices, releasing free dynamin dimers/tetramers and facilitating Arp2/3-mediated branched actin polymerization. The assembly/disassembly cycles of dynamin promote continuous actin bundling to generate mechanically stiff actin super-bundles. Super-resolution and immunogold platinum replica electron microscopy revealed dynamin along actin bundles at the fusogenic synapse. These findings implicate dynamin as a unique multifilament actin-bundling protein that regulates the dynamics and mechanical strength of the actin cytoskeletal network.

众所周知，发动蛋白 GTP 酶会束缚肌动蛋白丝，但其潜在的分子机制和生理相关性仍不清楚。我们的遗传分析揭示了动力蛋白在体内成肌细胞融合过程中推动侵入性膜突起的功能。使用生物化学、全内反射荧光显微镜、电子显微镜和低温电子断层扫描，我们发现动力蛋白在形成螺旋结构的同时将肌动蛋白束起来。在其最大容量时，每个动力螺旋在螺旋外缘捕获 12-16 条肌动蛋白丝。发动蛋白对 GTP 的水解会触发完全组装的发动蛋白螺旋的分解，释放出游离的发动蛋白二聚体/四聚体，并促进 Arp2/3 介导的支链肌动蛋白聚合。dynamin 的组装/拆卸循环促进连续的肌动蛋白捆绑，以产生机械僵硬的肌动蛋白超束。超分辨率和免疫金铂复制电子显微镜显示融合突触处沿着肌动蛋白束的动力蛋白。这些发现表明动力蛋白是一种独特的多丝肌动蛋白束缚蛋白，可调节肌动蛋白细胞骨架网络的动力学和机械强度。