Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate
Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate
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DOI：
10.1242/jcs.00381
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发表时间：
2003-05-01
影响因子：
4
通讯作者：
Yoshimori, T
中科院分区：
文献类型：
--
作者：
Mizushima, N;Kuma, A;Yoshimori, T
大自噬是将细胞质组分递送至溶酶体/空泡的主要细胞内降解系统。我们已经表明，在酵母和哺乳动物细胞中，Apg 12-Apg 5蛋白缀合物，这是由一个泛素样系统形成的，是必不可少的自噬体形成。在酵母中，Apg 12-Apg 5结合物与小卷曲螺旋蛋白Apg 16相互作用，形成类似于350 kDa的多聚体复合物。我们证明，小鼠Apg 12-Apg 5结合物形成类似于800 kDa的蛋白质复合物，含有一种新的WD重复蛋白。由于该新蛋白的N-末端区域与酵母Apg 16具有同源性，我们将其命名为小鼠Apg 16-like蛋白（Apg 16 L）。然而，Apg 16 L具有大的G末端结构域，其含有7个WD重复，这在酵母Apg 16中是不存在的。Apg 16 L与Apg 5和其他Apg 16 L单体相互作用;然而，两者都不依赖于WD重复结构域。与Apg 12-Apg 5一起，Apg 16 L在自噬体形成期间与自噬隔离膜缔合。由于这些特征与酵母Apg 16相似，我们得出结论Apg 16 L是酵母Apg 16的功能对应物。我们还发现Apg 16 L的膜靶向需要Apg 5而不是Apg 12。由于WD-重复序列蛋白为蛋白质-蛋白质相互作用提供了一个平台，因此预期类似于800 kDa的复合物在自噬体形成中起作用，进一步与哺乳动物细胞中的其他蛋白质相互作用。
Macroautophagy is the major intracellular degradation system delivering cytoplasmic components to the lysosome/vacuole. We have shown that, in yeast and mammalian cells, the Apg12-Apg5 protein conjugate, which is formed by a ubiquitin-like system, is essential for autophagosome formation. In yeast, the Apg12-Apg5 conjugate interacts with a small coiled-coil protein, Apg16, to form a similar to350 kDa multimeric complex. We demonstrate that the mouse Apg12-Apg5 conjugate forms a similar to800 kDa protein complex containing a novel WD-repeat protein. Because the N-terminal region of this novel protein shows homology with yeast Apg16, we have designated it mouse Apg16-like protein (Apg16L). Apg16L, however, has a large G terminal domain containing seven WD repeats that is absent from yeast Apg16. Apg16L interacts with both Apg5 and additional Apg16L monomers; neither interaction, however, depends on the WD-repeat domain. In conjunction with Apg12-Apg5, Apg16L associates with the autophagic isolation membrane for the duration of autophagosome formation. Because these features are similar to yeast Apg16, we concluded Apg16L is the functional counterpart of the yeast Apg16. We also found that membrane targeting of Apg16L requires Apg5 but not Apg12. Because WD-repeat proteins provide a platform for protein-protein interactions, the similar to800 kDa complex is expected to function in autophagosome formation, further interacting with other proteins in mammalian cells.