The Rab11-binding protein RELCH/KIAA1468 controls intracellular cholesterol distribution.
The Rab11-binding protein RELCH/KIAA1468 controls intracellular cholesterol distribution.
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DOI：
10.1083/jcb.201709123
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发表时间：
2018-05-07
期刊：
影响因子：
--
通讯作者：
Harada A
中科院分区：
文献类型：
--
作者：
Sobajima T;Yoshimura SI;Maeda T;Miyata H;Miyoshi E;Harada A
Sobajima等人鉴定了新蛋白质RICH/KIAA 1468作为Rab 11结合蛋白，并表明RICH/KIAA 1468和Rab 11调节从再循环内体到trans-Golgi网络的OSBP依赖性非囊泡胆固醇转运。胆固醇被内吞到晚期内体（LE）/溶酶体，通过囊泡和非囊泡转运机制被递送到其他细胞器。在这项研究中，我们讨论了一种新的机制，胆固醇转运从回收内体（RE）的trans-Golgi网络（TGN）通过的RABCH/KIAA 1468，这是在这项研究中新发现的Rab 11-GTP-和OSBP-结合蛋白。用25-羟基胆固醇处理细胞以诱导OSBP从细胞质迁移到TGN后，RE在TGN区域周围积累，但这种积累在OSBP或OSBP耗尽的细胞中减少。TGN中的胆固醇含量在Rab 11-、CD 3CH-和OSBP-耗尽的细胞中降低，而在LE/溶酶体中增加。根据体外重构实验，Rab 11结合的RE-like和OSBP结合的TGN-like脂质体，并促进OSBP依赖性胆固醇从RE-like转移到TGN-like脂质体。这些数据表明，EPOCH促进非囊泡胆固醇运输从RE的TGN通过膜系留。
Sobajima et al. identify the novel protein RELCH/KIAA1468 as a Rab11-binding protein and show that RELCH/KIAA1468 and Rab11 regulate OSBP-dependent nonvesicular cholesterol transport from recycling endosomes to the trans-Golgi network. Cholesterol, which is endocytosed to the late endosome (LE)/lysosome, is delivered to other organelles through vesicular and nonvesicular transport mechanisms. In this study, we discuss a novel mechanism of cholesterol transport from recycling endosomes (REs) to the trans-Golgi network (TGN) through RELCH/KIAA1468, which is newly identified in this study as a Rab11-GTP– and OSBP-binding protein. After treating cells with 25-hydroxycholesterol to induce OSBP relocation from the cytoplasm to the TGN, REs accumulated around the TGN area, but this accumulation was diminished in RELCH- or OSBP-depleted cells. Cholesterol content in the TGN was decreased in Rab11-, RELCH-, and OSBP-depleted cells and increased in the LE/lysosome. According to in vitro reconstitution experiments, RELCH tethers Rab11-bound RE-like and OSBP-bound TGN-like liposomes and promotes OSBP-dependent cholesterol transfer from RE-like to TGN-like liposomes. These data suggest that RELCH promotes nonvesicular cholesterol transport from REs to the TGN through membrane tethering.
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