Rab35 establishes the EHD1-association site by coordinating two distinct effectors during neurite outgrowth
Rab35 establishes the EHD1-association site by coordinating two distinct effectors during neurite outgrowth
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DOI：
10.1242/jcs.117846
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发表时间：
2013-06-01
影响因子：
4
通讯作者：
Fukuda, Mitsunori
中科院分区：
文献类型：
--
作者：
Kobayashi, Hotaka;Fukuda, Mitsunori
内吞再循环是已经内化的分子再循环回到质膜的过程，尽管它对于调节各种细胞事件至关重要，但该过程背后的分子联系仍然知之甚少。在这里，我们报告了两个看门人的内吞回收，分子开关Rab 35和分子剪刀EHD 1，这是由两个不同的Rab 35效应介导的PC 12细胞的神经突起生长过程中的分子连接。Rab 35与MICAL-L1和centaurin-beta 2/ACAP 2形成三重复合物，并响应神经生长因子刺激将它们募集到核周Arf 6阳性内体。然后，MICAL-L1和半人马座-β 2通过分别作为EHD 1的支架和Arf 6的灭活剂而协同地将EHD 1募集到相同的隔室。我们建议Rab 35通过整合两个不同Rab 35效应子的功能来调节Arf 6阳性内体上EHD 1-缔合位点的形成，以成功地实现神经突生长。
Endocytic recycling is a process in which molecules that have been internalized are recycled back to the plasma membrane, and although it is crucial for regulating various cellular events, the molecular nexus underlying this process remains poorly understood. Here we report a molecular link between two gatekeepers for endocytic recycling, the molecular switch Rab35 and the molecular scissors EHD1, that is mediated by two distinct Rab35 effectors during neurite outgrowth of PC12 cells. Rab35 forms a tripartite complex with MICAL-L1 and centaurin-beta 2/ACAP2 and recruits them to perinuclear Arf6-positive endosomes in response to nerve growth factor stimulation. MICAL-L1 and centaurin-beta 2 then cooperatively recruit EHD1 to the same compartment by functioning as a scaffold for EHD1 and as an inactivator of Arf6, respectively. We propose that Rab35 regulates the formation of an EHD1-association site on Arf6-positive endosomes by integrating the functions of two distinct Rab35 effectors for successful neurite outgrowth.