Numb regulates vesicular docking for homotypic fusion of early endosomes via membrane recruitment of Mon1b
Numb regulates vesicular docking for homotypic fusion of early endosomes via membrane recruitment of Mon1b
复制标题
Numb 通过 Mon1b 的膜募集调节早期内体同型融合的囊泡对接
DOI：
10.1038/cr.2016.34
复制
发表时间：
2016
期刊：
影响因子：
44.1
通讯作者：
Li Huashun
中科院分区：
文献类型：
--
作者：
Shao Ximing;Liu Yi;Yu Qian;Ding Zhihao;Qian Wenyu;Zhang Lei;Zhang Jianchao;Jiang Nan;Gui Linfei;Xu Zhiheng;Hong Yang;Ma Yifan;Wei Yanjie;Liu Xiaoqing;Jiang Changan;Zhu Minyan;Li Hongchang;Li Huashun
Numb 是一种内吞蛋白，在不对称细胞分裂、细胞迁移和分化等多种细胞过程中发挥着至关重要的作用。然而，人们对 Numb 调节内吞运输的分子机制知之甚少。在这里，我们证明 Numb 是早期内体 (EE) 同型融合的对接调节因子。 Numb 耗尽会导致聚集但未融合的 EE，这可以通过过表达胞质 Numb 65 和 Numb 71 而不是质膜附着的 Numb 66 或 Numb 72 来挽救。延时分析表明，在没有 Numb 的情况下，成对的囊泡倾向于束缚，但不会彼此融合。我们进一步表明 Numb 与另一个对接调节因子 Mon1b 结合，并且是将胞质 Mon1b 募集到 EE 膜所必需的。与此一致的是，Mon1b 的缺失会导致 EE 融合中出现类似的缺陷。因此，我们的研究确定了 Numb 通过介导 EE 融合来调节内吞分选的新机制。
Numb is an endocytic protein that plays crucial roles in diverse cellular processes such as asymmetric cell division, cell migration and differentiation. However, the molecular mechanism by which Numb regulates endocytic trafficking is poorly understood. Here, we demonstrate that Numb is a docking regulator for homotypic fusion of early endosomes (EEs). Numb depletion causes clustered but unfused EEs, which can be rescued by overexpressing cytosolic Numb 65 and Numb 71 but not plasma membrane-attached Numb 66 or Numb 72. Time-lapse analysis reveals that paired vesicles tend to tether but not fuse with each other in the absence of Numb. We further show that Numb binds to another docking regulator, Mon1b, and is required for the recruitment of cytosolic Mon1b to the EE membrane. Consistent with this, deletion of Mon1b causes similar defects in EE fusion. Our study thus identifies a novel mechanism by which Numb regulates endocytic sorting by mediating EE fusion.