Slow axonal transport driven by directional actin turnover

尽管肌动蛋白和相关蛋白对轴突的延伸是必不可少的，但它们是如何沿着轴突运输的仍不清楚。在这里，我们展示了肌动蛋白细丝(F-肌动蛋白)和相关蛋白通过定向肌动蛋白聚合/解聚(称为踏板磨)向轴突生长锥迁移。沿着轴突迁移的F-肌动蛋白经历了脚踏式碾磨，其聚合末端朝向生长锥体。F-肌动蛋白通过细胞黏附分子L1-CAM和连接蛋白Shootin1锚定在质膜上。F-肌动蛋白的迁移依赖于它们的聚合和底物锚定，并且在底物上检测到与F-肌动蛋白迁移相关的定向反作用力。肌动蛋白相关蛋白通过与纤维相互作用与F-肌动蛋白共同迁移。我们的发现揭示了一种新的细胞内运输方式，它向轴突前沿提供肌动蛋白和相关蛋白，从而促进其突起。

Although actin and associated proteins are essential for axonal extension, how they are transported along axons remains unclear. Here we show that actin filaments (F-actins) and associated proteins migrate toward the axonal growth cone by means of directional actin polymerization/depolymerization, called treadmilling. F-actins migrating along axonal shafts underwent treadmilling, with their polymerizing ends oriented toward the growth cone. F-actins were anchored to the plasma membrane through the cell adhesion molecule L1-CAM and the linker protein shootin1. Migration of F-actins depended on their polymerization and substrate anchorage, and directional counter-forces associated with F-actin migration were detected on the substrate. Actin-associated proteins co-migrated with F-actins by interacting with the filaments. Our findings reveal a new mode of intracellular transport, which supplies actin and associated proteins to the axonal leading edge, thereby promoting its protrusion.