Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages
Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages
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DOI：
10.1038/ncb1846
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发表时间：
2009-04-01
影响因子：
21.3
通讯作者：
Yoshimori, Tamotsu
中科院分区：
文献类型：
--
作者：
Matsunaga, Kohichi;Saitoh, Tatsuya;Yoshimori, Tamotsu
Beclin 1是自噬所必需的蛋白质，与hVps 34/III类磷脂酰肌醇-3-激酶和UVRAG结合。在这里，我们已经确定了两个Beclin 1相关蛋白，Atg 14 L和Rubicon。Atg 14 L和UVRAG以相互排斥的方式与Beclin 1结合，而Rubicon仅与UVRAG复合物的亚群结合;因此，存在三种不同的Beclin 1复合物。GFP-Atg 14 L定位于细胞的隔离膜和自噬体，以及内质网和未知点。敲除小鼠ES细胞中Atg 14 L导致自噬体形成缺陷。GFP-Rubicon定位于内体/溶酶体。Rubicon的敲除引起自噬的增强，特别是在成熟步骤，以及内吞运输的增强。这些数据表明，Beclin 1-hVps 34复合物通过改变亚基组成在自噬的两个不同步骤中起作用。
Beclin 1, a protein essential for autophagy, binds to hVps34/Class III phosphatidylinositol-3-kinase and UVRAG. Here, we have identified two Beclin 1 associated proteins, Atg14L and Rubicon. Atg14L and UVRAG bind to Beclin 1 in a mutually exclusive manner, whereas Rubicon binds only to a subpopulation of UVRAG complexes; thus, three different Beclin 1 complexes exist. GFP- Atg14L localized to the isolation membrane and autophagosome, as well as to the ER and unknown puncta. Knockout of Atg14L in mouse ES cells caused a defect in autophagosome formation. GFP-Rubicon was localized at the endosome/lysosome. Knockdown of Rubicon caused enhancement of autophagy, especially at the maturation step, as well as enhancement of endocytic trafficking. These data suggest that the Beclin 1-hVps34 complex functions in two different steps of autophagy by altering the subunit composition.