OATL1, a novel autophagosome-resident Rab33B-GAP, regulates autophagosomal maturation.
OATL1, a novel autophagosome-resident Rab33B-GAP, regulates autophagosomal maturation.
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DOI：
10.1083/jcb.201008107
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发表时间：
2011-03-07
期刊：
影响因子：
--
通讯作者：
Fukuda M
中科院分区：
文献类型：
--
作者：
Itoh T;Kanno E;Uemura T;Waguri S;Fukuda M
由Atg 8募集到自噬体的OATL 1差距活性调节自噬体-溶酶体融合。自噬是真核细胞中普遍存在的一种降解系统。泛素样蛋白Atg 8及其同源物是自噬体形成所必需的，并作为聚集蛋白和受损细胞器的选择性自噬的标志。在这项研究中，我们报告的证据表明，OATL 1，一个假定的Rab鸟苷三磷酸酶激活蛋白（GAP），是一种新的结合伴侣的Atg 8同系物在哺乳动物细胞。OATL 1通过与Atg 8同源物直接相互作用被募集到分离膜和自噬体，并通过其GAP活性参与自噬体和溶酶体之间的融合。我们进一步提供证据表明Rab 33 B是一种Atg 16 L1结合蛋白，是OATL 1的靶底物，与OATL 1一样参与自噬体和溶酶体之间的融合。由于OATL 1的GAP活性和Atg 8同源物结合活性都是OATL 1发挥功能所必需的，因此我们提出了一个模型，即OATL 1使用Atg 8同源物作为支架来发挥其GAP活性并调节自噬体成熟。
The GAP activity of OATL1, which is recruited to autophagosomes by Atg8, regulates autophagosome–lysosome fusion. Macroautophagy is a bulk degradation system conserved in all eukaryotic cells. A ubiquitin-like protein, Atg8, and its homologues are essential for autophagosome formation and act as a landmark for selective autophagy of aggregated proteins and damaged organelles. In this study, we report evidence demonstrating that OATL1, a putative Rab guanosine triphosphatase–activating protein (GAP), is a novel binding partner of Atg8 homologues in mammalian cells. OATL1 is recruited to isolation membranes and autophagosomes through direct interaction with Atg8 homologues and is involved in the fusion between autophagosomes and lysosomes through its GAP activity. We further provide evidence that Rab33B, an Atg16L1-binding protein, is a target substrate of OATL1 and is involved in the fusion between autophagosomes and lysosomes, the same as OATL1. Because both its GAP activity and its Atg8 homologue–binding activity are required for OATL1 to function, we propose a model that OATL1 uses Atg8 homologues as a scaffold to exert its GAP activity and to regulate autophagosomal maturation.
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