Retromer-driven membrane tubulation separates endosomal recycling from Rab7/Ypt7-dependent fusion.
Retromer-driven membrane tubulation separates endosomal recycling from Rab7/Ypt7-dependent fusion.
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DOI：
10.1091/mbc.e16-08-0582
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发表时间：
2017-03-15
影响因子：
3.3
通讯作者：
Ungermann C
中科院分区：
文献类型：
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作者：
Purushothaman LK;Arlt H;Kuhlee A;Raunser S;Ungermann C
Rab如何在回收和融合中发挥作用？SNX-BAR逆转录体的内体亚复合物可以结合Ypt 7并与HOPS复合物竞争。然后组装完整的逆转录酶导致Ypt 7的位移。这些数据解释了如何域的形成和Ypt 7参与可以协调。内体是内吞途径的主要蛋白分选中心。它们将注定要降解的蛋白质分类到内部囊泡中，同时通过管状载体将受体回收到高尔基体。肾小管形成依赖于Rab 7/Ypt 7相互作用的逆转录聚合物复合物，其由分选连接蛋白二聚体（SNX-BAR）和三聚体货物选择复合物（CSC）组成。成熟核内体与溶酶体样液泡的融合也需要Rab 7/Ypt 7。在这里，我们解决了一个主要的问题，在理解这种双重功能的内体Rab 7/Ypt 7，使用一个完全重建的系统，包括纯化的，全长酵母SNX-BAR和CSC，其整体结构，我们目前。我们发现，膜活性SNX-BAR复合物在再循环小管形成期间从货物结合的CSC中置换Ypt 7。这解释了单个Rab如何协调内体上的再循环和融合。
How does a Rab function in both recycling and fusion? An endosomal subcomplex of the SNX-BAR retromer can bind to Ypt7 and compete with the HOPS complex. Assembly of the full retromer then results in displacement of Ypt7. These data explain how domain formation and Ypt7 participation can be coordinated. Endosomes are the major protein-sorting hubs of the endocytic pathway. They sort proteins destined for degradation into internal vesicles while in parallel recycling receptors via tubular carriers back to the Golgi. Tubule formation depends on the Rab7/Ypt7-interacting retromer complex, consisting of the sorting nexin dimer (SNX-BAR) and the trimeric cargo selection complex (CSC). Fusion of mature endosomes with the lysosome-like vacuole also requires Rab7/Ypt7. Here we solve a major problem in understanding this dual function of endosomal Rab7/Ypt7, using a fully reconstituted system, including purified, full-length yeast SNX-BAR and CSC, whose overall structure we present. We reveal that the membrane-active SNX-BAR complex displaces Ypt7 from cargo-bound CSC during formation of recycling tubules. This explains how a single Rab can coordinate recycling and fusion on endosomes.