Orso Genny, Pendin Diana, Liu Song, Tosetto Jessica, Moss Tyler J, Faust Joseph E, Micaroni Massimo, Egorova Anastasia, Martinuzzi Andrea, McNew James A, Daga Andrea
Eugenio Medea Scientific Institute, Conegliano 31015, Italy.
Nature. 2009 Aug 20;460(7258):978-83. doi: 10.1038/nature08280. Epub 2009 Jul 26.
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.
内质网（ER）功能的正常发挥离不开其正确结构的建立与维持。内质网的生物发生和维持需要同型膜融合，并且已证明这依赖于GTP水解。在此，我们证明果蝇Atlastin（果蝇中与参与遗传性痉挛性截瘫的哺乳动物GTP酶atlastin 1同源的蛋白）定位于内质网膜上，其缺失会导致内质网片段化。嵌入不同膜中的果蝇Atlastin能够形成反式寡聚复合物，其过表达会诱导内质网轮廓增大，这与内质网膜过度融合一致。体外实验证实Atlastin以GTP依赖的方式自主驱动膜融合。相反，缺乏GTP酶活性的Atlastin无活性，由于无法自我缔合而不能形成反式寡聚复合物，并且在体外无法促进融合。这些结果表明Atlastin介导膜系留和融合，并有力地表明内质网同型融合需要GTP酶活性。
