Endocytic cargos are transported to recycling endosomes (RE) but how these sorting platforms are generated is not well understood. Here we describe our biochemical and live imaging studies of the conserved MON2-DOPEY complex in RE formation. MON2 mainly co-localized with RE marker RAB4B in peripheral dots and perinuclear region. The peripheral RE approached, interacted with, and separated from sorting nexin 3 (SNX3)-positive early endosomes (EE). Membrane-bound DOPEY2 was recruited to RE dependent upon MON2 expression, and showed binding abilities to kinesin and dynein/dynactin motor proteins. MON2-knockout impaired segregation of RE from EE and led to a decreased tubular recycling endosomal network, whereas RE was accumulated at perinuclear regions in DOPEY2-knockout cells. MON2 depletion also impaired intracellular transferrin receptor recycling, as well as retrograde transport of Wntless during its passage through RE before delivery from EE to the Golgi. Together, these data suggest that the MON2 drives separation of RE from EE and is required for efficient transport of endocytic cargo molecules.Key words: membrane trafficking, MON2, recycling endosomes, Wntless.

中文翻译：

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MON2 通过回收内体引导无休止运输至高尔基体。


内吞货物被运输到回收内体（RE），但这些分选平台是如何产生的尚不清楚。在这里，我们描述了对 RE 形成中保守的 MON2-DOPEY 复合物的生化和实时成像研究。 MON2 主要与 RE 标记 RAB4B 共定位于外围点和核周区域。外周 RE 接近、相互作用并与分选 nexin 3 (SNX3) 阳性的早期内涵体 (EE) 分离。膜结合的 DOPEY2 根据 MON2 表达被招募到 RE，并显示出与驱动蛋白和动力蛋白/动力蛋白运动蛋白的结合能力。 MON2 敲除损害了 RE 与 EE 的分离，导致管状循环内体网络减少，而 RE 在 DOPEY2 敲除细胞的核周区域积累。 MON2 耗竭还会损害细胞内转铁蛋白受体的再循环，以及 Wntless 在从 EE 输送到高尔基体之前通过 RE 的过程中的逆行转运。总之，这些数据表明 MON2 驱动 RE 与 EE 的分离，并且是内吞货物分子有效运输所必需的。关键词：膜运输，MON2，回收内体，Wntless。