GOP-1 promotes apoptotic cell degradation by activating the small GTPase Rab2 in C. elegans.
GOP-1 promotes apoptotic cell degradation by activating the small GTPase Rab2 in C. elegans.
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DOI：
10.1083/jcb.201610001
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发表时间：
2017-06-05
期刊：
影响因子：
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通讯作者：
Wang X
中科院分区：
文献类型：
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作者：
Yin J;Huang Y;Guo P;Hu S;Yoshina S;Xuan N;Gan Q;Mitani S;Yang C;Wang X
Rab2调节多个膜的运输过程，但它如何被招募到靶膜并在其上被激活仍不清楚。在这里，殷等人。确定一种保守的蛋白质GOP-1，它激活UNC-108/Rab2以促进吞噬小体、内小体和DCV的成熟。由细胞程序性死亡产生的凋亡细胞被吞噬细胞吞噬，并被质膜来源的吞噬小体包裹。吞噬小体的成熟涉及一系列的膜重塑事件，这些事件由Rab GTP酶的连续作用控制，并导致吞噬小体的形成，在那里细胞身体被降解。在这里，我们确定GOP-1是秀丽隐杆线虫中一种新的细胞凋亡清除调节因子。GOP-1的丢失通过RAb-5阳性阶段影响吞噬小体成熟，导致吞噬小体酸化和吞噬溶酶体形成缺陷，表型与UNC-108相同，不受失去的线虫Rab2的影响。GOP-1暂时与含有身体的细胞吞噬小体结合，其功能的丧失使UNC-108的吞噬小体结合丧失。GOP-1与GDP结合和无核苷酸的UNC-108/Rab2相互作用，破坏GDI-UNC-108复合体，促进UNC-108/Rab2的激活和膜募集。GOP-1的缺失也取消了UNC-108与内小体的结合，导致内小体缺陷和致密的核心囊泡成熟。因此，GOP-1在多个过程中是UNC-108/Rab2的激活剂。
Rab2 regulates multiple membrane traffic processes, but how it is recruited to and activated on the target membrane remains unclear. Here, Yin et al. identify a conserved protein, GOP-1, that activates UNC-108/Rab2 to promote phagosome, endosome, and DCV maturation. Apoptotic cells generated by programmed cell death are engulfed by phagocytes and enclosed within plasma membrane–derived phagosomes. Maturation of phagosomes involves a series of membrane-remodeling events that are governed by the sequential actions of Rab GTPases and lead to formation of phagolysosomes, where cell corpses are degraded. Here we identified gop-1 as a novel regulator of apoptotic cell clearance in Caenorhabditis elegans. Loss of gop-1 affects phagosome maturation through the RAB-5–positive stage, causing defects in phagosome acidification and phagolysosome formation, phenotypes identical to and unaffected by loss of unc-108, the C. elegans Rab2. GOP-1 transiently associates with cell corpse–containing phagosomes, and loss of its function abrogates phagosomal association of UNC-108. GOP-1 interacts with GDP-bound and nucleotide-free UNC-108/Rab2, disrupts GDI-UNC-108 complexes, and promotes activation and membrane recruitment of UNC-108/Rab2 in vitro. Loss of gop-1 also abolishes association of UNC-108 with endosomes, causing defects in endosome and dense core vesicle maturation. Thus, GOP-1 is an activator of UNC-108/Rab2 in multiple processes.