Department of Molecular Biotechnology and Health Sciences. Molecular Biotechnology Center, University of Turin, Torino, Italy.
Department of Applied Science and Technology, Politecnico di Torino, Torino, Italy.
Nat Chem Biol. 2018 Aug;14(8):801-810. doi: 10.1038/s41589-018-0086-4. Epub 2018 Jun 18.
Directional transport of recycling cargo from early endosomes (EE) to the endocytic recycling compartment (ERC) relies on phosphatidylinositol 3-phosphate (PtdIns(3)P) hydrolysis and activation of the small GTPase Rab11. However, how these events are coordinated is yet unclear. By using a novel genetically-encoded FRET biosensor for Rab11, we report that generation of endosomal PtdIns(3)P by the clathrin-binding phosphoinositide 3-kinase class 2 alpha (PI3K-C2α) controls the activation of Rab11. Active Rab11, in turn, prompts the recruitment of the phosphatidylinositol 3-phosphatase myotubularin 1 (MTM1), eventually enabling the release of recycling cargo from the EE and its delivery toward the ERC. Our findings thus define that delivery of recycling cargo toward the ERC requires spatial and sequential coupling of Rab11 activity with PtdIns(3)P turnover.
从早期内涵体（EE）到内体再循环隔室（ERC）的回收货物的定向运输依赖于磷酸肌醇 3-磷酸（PtdIns（3）P）水解和小 GTPase Rab11 的激活。然而，这些事件如何协调尚不清楚。通过使用新型基因编码的 Rab11 FRET 生物传感器，我们报告说网格蛋白结合的磷酸肌醇 3-激酶类 2α（PI3K-C2α）产生内体 PtdIns（3）P 控制 Rab11 的激活。反过来，活性 Rab11 促使肌浆球蛋白 1（MTM1）的磷酯酰肌醇 3-磷酸酶的募集，最终使回收货物从 EE 释放并递送至 ERC。因此，我们的发现定义了回收货物递送至 ERC 需要 Rab11 活性与 PtdIns（3）P 周转的空间和顺序偶联。
