SUMOylation of EHD3 Modulates Tubulation of the Endocytic Recycling Compartment.
SUMOylation of EHD3 Modulates Tubulation of the Endocytic Recycling Compartment.
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EHD3的Sumoylation调节内吞回收室的管道。
DOI：
10.1371/journal.pone.0134053
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Horowitz M
中科院分区：
文献类型：
--
作者：
Cabasso O;Pekar O;Horowitz M
内吞作用定义了分子或大分子通过质膜的进入以及细胞中的膜运输。它依赖于大量的蛋白质进行蛋白质-蛋白质和蛋白质-磷脂相互作用。EH结构域蛋白（EHDs）组成一个家族，其成员参与胞吞的不同阶段.在四种哺乳动物EHD（EHD 1-EHD 4）中，EHD 1和EHD 3控制到内吞再循环室（ERC）和从ERC到质膜的交通，而EHD 2调节内化。最近，我们已经表明，EHD 2经历SUMO化，这有助于它从细胞核中退出，在那里它作为一个辅助阻遏物。在本研究中，我们测试了EHD 3是否经历SUMO化以及它在内吞再循环中的作用。我们表明，在体外和细胞培养中，EHD 3经历SUMO化。EHD 3定位于ERC的管状结构取决于其在赖氨酸315和511上的SUMO化。EHD 3的SUMO化的缺失对其二聚化没有影响，二聚化是EHD 3膜定位的重要因素，但对其在管状ERC结构中的出现具有显性负效应。非SUMO化的EHD 3延迟转铁蛋白从ERC再循环到细胞表面。我们的研究结果表明，SUMO化的EHD 3参与的ERC膜，这是很重要的有效回收。
Endocytosis defines the entry of molecules or macromolecules through the plasma membrane as well as membrane trafficking in the cell. It depends on a large number of proteins that undergo protein-protein and protein-phospholipid interactions. EH Domain containing (EHDs) proteins formulate a family, whose members participate in different stages of endocytosis. Of the four mammalian EHDs (EHD1-EHD4) EHD1 and EHD3 control traffic to the endocytic recycling compartment (ERC) and from the ERC to the plasma membrane, while EHD2 modulates internalization. Recently, we have shown that EHD2 undergoes SUMOylation, which facilitates its exit from the nucleus, where it serves as a co-repressor. In the present study, we tested whether EHD3 undergoes SUMOylation and what is its role in endocytic recycling. We show, both in-vitro and in cell culture, that EHD3 undergoes SUMOylation. Localization of EHD3 to the tubular structures of the ERC depends on its SUMOylation on lysines 315 and 511. Absence of SUMOylation of EHD3 has no effect on its dimerization, an important factor in membrane localization of EHD3, but has a dominant negative effect on its appearance in tubular ERC structures. Non-SUMOylated EHD3 delays transferrin recycling from the ERC to the cell surface. Our findings indicate that SUMOylation of EHD3 is involved in tubulation of the ERC membranes, which is important for efficient recycling.