Rab2 promotes autophagic and endocytic lysosomal degradation.
Rab2 promotes autophagic and endocytic lysosomal degradation.
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DOI：
10.1083/jcb.201611027
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发表时间：
2017-07-03
期刊：
影响因子：
--
通讯作者：
Juhász G
中科院分区：
文献类型：
--
作者：
Lőrincz P;Tóth S;Benkő P;Lakatos Z;Boda A;Glatz G;Zobel M;Bisi S;Hegedűs K;Takáts S;Scita G;Juhász G
Rab7促进自噬小体和晚期内噬小体与溶酶体的融合。L、ő、林茨等人。结果表明，Rab2对于将自噬和内吞的货物运送到溶酶体和它们的降解至关重要，并且它促进了自噬小体和溶酶体的融合。结果提示，Rab2和Rab7协同促进自噬和内体降解以及溶酶体功能。在酵母和后生动物细胞中，Rab7促进自噬小体和晚期内噬菌体与溶酶体的融合，并与其效应器--系留复合体啤酒花共同作用。在这里，我们展示了另一个小的GTP酶，Rab2，也是果蝇自噬小体和内小体成熟和正常的溶酶体功能所必需的。我们证明了Rab2与啤酒花结合，并且其活性的、GTP锁定的形式与自溶酶体相关。重要的是，与GTP锁定的Rab7不同，活性Rab2的表达促进了自溶酶体的融合，这表明其数量通常是限速的。我们还证明RAB2A是人类乳腺癌细胞清除自噬小体所必需的。综上所述，我们认为Rab2是自噬和内吞货物运送到溶酶体和降解溶酶体的关键因素。
Rab7 promotes fusion of autophagosomes and late endosomes with lysosomes. Lőrincz et al. show that Rab2 is critical for the delivery of autophagic and endocytic cargo to lysosomes and for their degradation, and that it promotes autophagosome–lysosome fusion. The results suggest Rab2 and Rab7 coordinately promote autophagic and endosomal degradation and lysosome function. Rab7 promotes fusion of autophagosomes and late endosomes with lysosomes in yeast and metazoan cells, acting together with its effector, the tethering complex HOPS. Here we show that another small GTPase, Rab2, is also required for autophagosome and endosome maturation and proper lysosome function in Drosophila melanogaster. We demonstrate that Rab2 binds to HOPS, and that its active, GTP-locked form associates with autolysosomes. Importantly, expression of active Rab2 promotes autolysosomal fusions unlike that of GTP-locked Rab7, suggesting that its amount is normally rate limiting. We also demonstrate that RAB2A is required for autophagosome clearance in human breast cancer cells. In conclusion, we identify Rab2 as a key factor for autophagic and endocytic cargo delivery to and degradation in lysosomes.