Atg14 and UVRAG Mutually exclusive subunits of mammalian Beclin 1-PI3K complexes
Atg14 and UVRAG Mutually exclusive subunits of mammalian Beclin 1-PI3K complexes
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DOI：
10.4161/auto.5.4.8062
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发表时间：
2009-05-16
期刊：
影响因子：
13.3
通讯作者：
Mizushima, Noboru
中科院分区：
文献类型：
--
作者：
Itakura, Eisuke;Mizushima, Noboru
Vps34是III类磷脂酰肌醇3-激酶（pi3 -激酶），产生磷脂酰肌醇3磷酸（PI3P），并在多种膜交通途径中发挥作用，包括内吞作用、多泡体形成和自噬。在哺乳动物细胞中，Vps34与Beclin 1形成复合物，但目前尚不清楚Vps34复合物如何在每个膜运输途径上发挥其特定功能。我们最近使用计算方法确定了哺乳动物Atg14，这是Vps34-Beclin 1复合物的一个新的结合伙伴。Atg14复合体由Vps34、Beclin 1和p150组成，但缺乏UVRAG，此前报道过UVRAG可以结合Vps34-Beclin 1复合体。饥饿时，Atg14定位于隔离膜/吞噬细胞，是自噬体形成的必要条件。相比之下，UVRAG主要定位于晚期核内体。由于UVRAG与酵母Vps38具有同源性，我们推测它可能是哺乳动物Vps38的同源物。这些发现表明Vps34-Beclin 1复合物至少有两种不同的功能，可以通过其结合伙伴Atg14和UVRAG促进。
Vps34, a Class III phosphatidylinositol 3-kinase (PI3-kinase), produces phosphatidylinositol 3 phosphate (PI3P) and functions in various membrane traffic pathways including endocytosis, multivesicular body formation and autophagy. In mammalian cells, Vps34 forms a complex with Beclin 1, but it remains unclear how this Vps34 complex exerts its specific function on each membrane trafficking pathway. We recently identified mammalian Atg14, a new binding partner of the Vps34-Beclin 1 complex, using a computational approach. The Atg14 complex consists of Vps34, Beclin 1 and p150, but lacks UVRAG, which was previously reported to bind the Vps34-Beclin 1 complex. Atg14 localizes to isolation membrane/phagophore during starvation and is essential for autophagosome formation. In contrast, UVRAG primarily localizes to late endosomes. Since UVRAG shows homology with yeast Vps38, we speculate that it could be a mammalian Vps38 ortholog. These findings indicate that the Vps34-Beclin 1 complex has at least two distinct functions, which can be promoted by its binding partners Atg14 and UVRAG.