Homotypic fusion of ER membranes requires the dynamin-like GTPase Atlastin
Homotypic fusion of ER membranes requires the dynamin-like GTPase Atlastin
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DOI：
10.1038/nature08280
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发表时间：
2009-08-20
期刊：
影响因子：
64.8
通讯作者：
Daga, Andrea
中科院分区：
文献类型：
--
作者：
Orso, Genny;Pendin, Diana;Daga, Andrea
正确结构的建立和维持对于内质网 (ER) 功能至关重要。同型膜融合是 ER 生物发生和维持所必需的，并且已被证明依赖于 GTP 水解。在这里，我们证明果蝇阿特拉斯汀（参与遗传性痉挛性截瘫的哺乳动物 GTP 酶阿特拉斯汀 1 的果蝇同源物）定位于内质网膜上，并且它的缺失会导致内质网碎片。嵌入不同膜中的果蝇 Atlastin 能够形成反式寡聚复合物，其过度表达会导致 ER 谱扩大，这与 ER 膜的过度融合一致。体外实验证实 Atlastin 以 GTP 依赖性方式自主驱动膜融合。相比之下，GTPase 缺陷的 Atlastin 则无活性，由于无法自缔合而无法形成反式寡聚复合物，并且无法在体外促进融合。这些结果证明 Atlastin 介导膜束缚和融合，并强烈表明 GTP 酶活性是 ER 同型融合所需的。
Establishment and maintenance of proper architecture is essential for endoplasmic reticulum (ER) function. Homotypic membrane fusion is required for ER biogenesis and maintenance, and has been shown to depend on GTP hydrolysis. Here we demonstrate that Drosophila Atlastin-the fly homologue of the mammalian GTPase atlastin 1 involved in hereditary spastic paraplegia-localizes on ER membranes and that its loss causes ER fragmentation. Drosophila Atlastin embedded in distinct membranes has the ability to form trans-oligomeric complexes and its overexpression induces enlargement of ER profiles, consistent with excessive fusion of ER membranes. In vitro experiments confirm that Atlastin autonomously drives membrane fusion in a GTP-dependent fashion. In contrast, GTPase-deficient Atlastin is inactive, unable to form trans-oligomeric complexes owing to failure to self-associate, and incapable of promoting fusion in vitro. These results demonstrate that Atlastin mediates membrane tethering and fusion and strongly suggest that it is the GTPase activity that is required for ER homotypic fusion.