The microtubule motor dynein mediates polarised trafficking of a wide variety of organelles, vesicles and macromolecules. These functions are dependent on the dynactin complex, which helps recruit cargoes to dynein's tail and activates motor movement. How the dynein-dynactin complex orchestrates trafficking of diverse cargoes is unclear. Here, we identify HEATR5B, an interactor of the adaptor protein-1 (AP1) clathrin adaptor complex, as a novel player in dynein-dynactin function. HEATR5B was recovered in a biochemical screen for proteins whose association with the dynein tail is augmented by dynactin. We show that HEATR5B binds directly to the dynein tail and dynactin and stimulates motility of AP1-associated endosomal membranes in human cells. We also demonstrate that the Drosophila HEATR5B homologue is an essential gene that selectively promotes dynein-based transport of AP1-bound membranes to the Golgi apparatus. As HEATR5B lacks the coiled-coil architecture typical of dynein adaptors, our data point to a non-canonical process orchestrating motor function on a specific cargo. We additionally show that HEATR5B promotes association of AP1 with endosomal membranes independently of dynein. Thus, HEATR5B co-ordinates multiple events in AP1-based trafficking.

中文翻译：

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HEATR5B 与动力蛋白-动力蛋白结合并促进 AP1 结合的内体膜的运动

微管运动动力蛋白介导多种细胞器、囊泡和大分子的极化运输。这些功能依赖于动力蛋白复合物，它有助于将货物招募到动力蛋白的尾部并激活运动。动力蛋白-动力蛋白复合物如何协调不同货物的运输尚不清楚。在这里，我们将接头蛋白 1 (AP1) 网格蛋白接头复合物的相互作用蛋白 HEATR5B 确定为动力蛋白-动力蛋白功能的新参与者。HEATR5B 在生化筛选中被回收，以寻找与动力蛋白尾部的关联被动力蛋白增强的蛋白质。我们发现 HEATR5B 直接与动力蛋白尾部和动力蛋白结合，并刺激人类细胞中 AP1 相关内体膜的运动性。我们还证明，果蝇HEATR5B 同源物是一个必需基因，它选择性地促进基于动力蛋白的 AP1 结合膜向高尔基体的转运。由于 HEATR5B 缺乏动力蛋白适配器典型的螺旋线圈架构，我们的数据表明在特定货物上协调运动功能的非规范过程。我们还表明，HEATR5B 独立于动力蛋白促进 AP1 与内体膜的结合。因此，HEATR5B 协调基于 AP1 的贩运中的多个事件。