The Rab GTPase Ypt7 is linked to retromer-mediated receptor recycling and fusion at the yeast late endosome
The Rab GTPase Ypt7 is linked to retromer-mediated receptor recycling and fusion at the yeast late endosome
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DOI：
10.1242/jcs.071977
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发表时间：
2010-12-01
影响因子：
4
通讯作者：
Ungermann, Christian
中科院分区：
文献类型：
--
作者：
Balderhaar, Henning J. Kleine;Arlt, Henning;Ungermann, Christian
细胞膜系统的细胞器需要平衡裂变和聚变事件以维持其表面体积比。在哺乳动物晚期内体中，Rab GTPase Rab7是融合的主要调节因子，而同源酵母蛋白Ypt7似乎仅限于液泡表面。在这里，我们提供的证据表明，Ypt7被招募到并作用于晚期核内体，在那里它影响多种运输反应。我们发现，Ypt7的过表达导致液泡膜的膨胀和大量内陷，这需要Ypt7在GDP和gtp结合状态之间循环。内陷可被ESCRT、CORVET和逆转录突变体阻断，但不能被自噬或AP-3突变体阻断。我们还发现，Ypt7- gtp特异性地与后转录物识别亚复合物结合，该亚复合物与它的货物Vps10一样，在Ypt7过量生产时存在于液泡上。我们的数据表明，Ypt7在后期核内体中发挥作用，协调后转录物介导的再循环与后期核内体与液泡的融合。
Organelles of the endomembrane system need to counterbalance fission and fusion events to maintain their surface-to-volume ratio. At the late mammalian endosome, the Rab GTPase Rab7 is a major regulator of fusion, whereas the homologous yeast protein Ypt7 seems to be restricted to the vacuole surface. Here, we present evidence that Ypt7 is recruited to and acts on late endosomes, where it affects multiple trafficking reactions. We show that overexpression of Ypt7 results in expansion and massive invagination of the vacuolar membrane, which requires cycling of Ypt7 between GDP- and GTP-bound states. Invaginations are blocked by ESCRT, CORVET and retromer mutants, but not by autophagy or AP-3 mutants. We also show that Ypt7-GTP specifically binds to the retromer cargo-recognition subcomplex, which - like its cargo Vps10 - is found on the vacuole upon Ypt7 overproduction. Our data suggest that Ypt7 functions at the late endosome to coordinate retromer-mediated recycling with the fusion of late endosomes with vacuoles.