Autophagy-related protein 9 (ATG9) is a transmembrane protein component of the autophagy machinery that cycles between the trans-Golgi network (TGN) in the perinuclear area and other compartments in the peripheral area of the cell. In mammalian cells, export of the ATG9A isoform from the TGN into ATG9A-containing vesicles is mediated by the adaptor protein 4 (AP-4) complex. However, the mechanisms responsible for the subsequent distribution of these vesicles to the cell periphery is unclear. Herein we show that the AP-4–accessory protein RUSC2 couples ATG9A-containing vesicles to the plus-end-directed microtubule motor kinesin-1 via an interaction between a disordered region of RUSC2 and the kinesin-1 light chain (KLC). This interaction is counteracted by the microtubule-associated WD40-repeat domain 47 protein (WDR47). These findings uncover a mechanism for the peripheral distribution of ATG9A-containing vesicles, involving the function of RUSC2 as a kinesin-1 adaptor and WDR47 as a negative regulator of this function.

自噬相关蛋白 9 (ATG9) 是自噬机制的跨膜蛋白成分，在跨膜之间循环。-核周区域的高尔基网络 (TGN) 和细胞外围区域的其他隔室。在哺乳动物细胞中，ATG9A 异构体从 TGN 输出到含有 ATG9A 的囊泡中是由衔接蛋白 4 (AP-4) 复合物介导的。然而，这些囊泡随后分布到细胞外围的机制尚不清楚。在这里，我们展示了 AP-4 辅助蛋白 RUSC2 通过 RUSC2 的无序区域和 kinesin-1 轻链 (KLC) 之间的相互作用将含有 ATG9A 的囊泡与加端定向微管运动 kinesin-1 偶联。这种相互作用被微管相关的 WD40 重复结构域 47 蛋白 (WDR47) 抵消。这些发现揭示了含 ATG9A 的囊泡外周分布的机制，