Identification of the Switch in Early-to-Late Endosome Transition
Identification of the Switch in Early-to-Late Endosome Transition
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DOI：
10.1016/j.cell.2010.03.011
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发表时间：
2010-04-30
期刊：
影响因子：
64.5
通讯作者：
Spang, Anne
中科院分区：
文献类型：
--
作者：
Poteryaev, Dmitry;Datta, Sunando;Spang, Anne
从早期内体到晚期内体的顺序转运需要小 GTPases Rab5 和 Rab7 的协调活动。早期内体和晚期内体之间的转变可以通过转运载体或通过 Rab 转化来介导，在这一过程中，Rab5 从内体中的丢失与 Rab7 的获得同时发生。我们证明 Rab 转化是蛋白质从秀丽隐杆线虫体腔细胞早期内体传递到晚期内体的机制。此外，我们确定 SAND-1/Mon1 是后生动物 Rab 转化的关键开关。 SAND-1 在此过程中发挥双重作用。首先，它通过从内体膜上置换 RABX-5 来中断 RAB-5 激活的正反馈回路；其次，它可能通过与同一膜上的 HOPS 复合物相互作用来招募 RAB-7。因此，SAND-1/Mon1 通过控制 RAB-5 和 RAB-7 GEF 的定位充当开关。
Sequential transport from early to late endosomes requires the coordinated activities of the small GTPases Rab5 and Rab7. The transition between early and late endosomes could be mediated either through transport carriers or by Rab conversion, a process in which the loss of Rab5 from an endosome occurs concomitantly to the acquisition of Rab7. We demonstrate that Rab conversion is the mechanism by which proteins pass from early to late endosomes in Caenorhabditis elegans coelomocytes. Moreover, we identified SAND-1/Mon1 as the critical switch for Rab conversion in metazoa. SAND-1 serves a dual role in this process. First, it interrupts the positive feedback loop of RAB-5 activation by displacing RABX-5 from endosomal membranes; second, it times the recruitment of RAB-7, probably through interaction with the HOPS complex to the same membranes. SAND-1/Mon1 thus acts as a switch by controlling the localization of RAB-5 and RAB-7 GEFs.