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首页> 外文期刊>Biology Open >Apolipoprotein L9 interacts with LC3/GABARAP and is a microtubule-associated protein with a widespread subcellular distribution
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Apolipoprotein L9 interacts with LC3/GABARAP and is a microtubule-associated protein with a widespread subcellular distribution

机译:载脂蛋白L9与LC3 / GABARAP相互作用,是一种微管相关蛋白,具有广泛的亚细胞分布

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Mouse Apolipoprotein L9 is a 34-kDa phosphatidylethanolamine (PE)-binding protein. The gene is present only in mouse and rat genomes; hence it is restricted to two species. To understand why, it is essential to uncover details about its functions in cellular processes. Here we show that ApoL9 interacts with the proteins of the LC3 and GABARAP subfamilies, which are key players in macroautophagy.In vitrobinding studies show a strong association with GABARAP, and in amino acid-starved cells it preferentially interacts with lipidated LC3B, likely by binding to its PE moiety through its lipid-binding domain. On treatment with autophagy inhibitors bafilomycin A1 and chloroquine, ApoL9 is found near swollen mitochondria and on lysosomes/LAMP1-positive compartments. However, ApoL9 itself does not seem to be degraded as a result of autophagy, suggesting that it is not an autophagy cargo receptor. Deletions in a putative transmembrane region between amino acids 110 and 145 abolish binding to PE. In addition, ApoL9 can redistribute to stress granules, can homo-oligomerize, and is a microtubule-associated protein. In short, its distribution in the cell is quite widespread, suggesting that it could have functions at the intersection of membrane binding and reorganization, autophagy, cellular stress and intracellular lipid transport.This article has an associated First Person interview with the first author of the paper.
机译:小鼠载脂蛋白L9是一种34 kDa的磷脂酰乙醇胺(PE)结合蛋白。该基因仅存在于小鼠和大鼠基因组中。因此它仅限于两种。要了解原因,必须揭示有关其在细胞过程中功能的细节。在这里,我们显示ApoL9与LC3和GABARAP亚家族的蛋白质相互作用,而后者是宏观自噬的关键参与者。体外结合研究显示与GABARAP有很强的联系,在氨基酸缺乏的细胞中,它可能与脂化的LC3B优先相互作用通过其脂质结合结构域与其PE部分结合。用自噬抑制剂巴氟霉素A1和氯喹治疗后,在线粒体肿胀附近和溶酶体/ LAMP1阳性区室发现ApoL9。但是,ApoL9本身似乎并未因自噬而降解,表明它不是自噬货物受体。在氨基酸110和145之间的假定跨膜区域中的缺失消除了与PE的结合。此外,ApoL9可以重新分布到应激颗粒,可以均聚,并且是与微管相关的蛋白。简而言之,它在细胞中的分布非常广泛,这表明它可能在膜结合和重组,自噬,细胞应激和细胞内脂质转运的相交处起作用。本文接受了第一人称与第一人的采访纸。

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