Role of Hrs in maturation of autophagosomes in mammalian cells
Role of Hrs in maturation of autophagosomes in mammalian cells
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DOI：
10.1016/j.bbrc.2007.06.105
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发表时间：
2007-09-07
影响因子：
3.1
通讯作者：
Sugamura, Kazuo
中科院分区：
文献类型：
--
作者：
Tamai, Keiichi;Tanaka, Nobuyuki;Sugamura, Kazuo
自噬是一个进化上保守的系统，负责细胞成分的降解，有助于氨基酸池的增加，细胞器的更新和细胞内细菌的消除。自噬的分子过程尚不清楚。本研究表明，Hrs是内体蛋白分选的主要调节因子，在非特异性蛋白和化脓性链球菌的自噬降解中起着关键作用。我们发现含有FYVE结构域的Hrs定位于自噬体。通过自噬体标记LC3和溶酶体标记LAMP-1的共定位检测，Hrs耗损导致成熟自噬体（自噬溶酶体）数量显著减少。相比之下，原代自噬体的形成，通过LC3免疫印迹和非特异性蛋白的溶酶体降解检测，没有明显改变Hrs消耗。基于这些结果，我们提出了一种新的Hrs功能，它在自噬体成熟过程中起着至关重要的作用。(c) 2007爱思唯尔公司版权所有。
Autophagy is an evolutionarily conserved system responsible for the degradation of cellular components and contributes to the increasing of amino acid pool, organelle turnover, and elimination of intracellular bacteria. The molecular process of autophagy is still unclear. Here we demonstrate that Hrs, a master regulator in endosomal protein sorting, plays critical roles for the autophagic degradation of non-specific proteins and Streptococcus pyogenes. We found that Hrs containing FYVE domain is localized to autophagosomes. Hrs depletion resulted in a significant decrease in the number of mature autophagosomes (autophagolysosomes) detected by the co-localization of autophagosome marker LC3 and lysosome marker LAMP-1. In contrast, formation of the primary autophagosome, detected by LC3 immunoblotting and lysosomal degradation of non-specific proteins, were not significantly altered by Hrs depletion. Based on these results, we propose a novel function of Hrs, as a crucial player in the maturation of autophagosomes. (c) 2007 Elsevier Inc. All rights reserved.