ER exit sites are physical and functional core autophagosome biogenesis components.
ER exit sites are physical and functional core autophagosome biogenesis components.
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DOI：
10.1091/mbc.e13-07-0381
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发表时间：
2013-09
影响因子：
3.3
通讯作者：
Nunnari J
中科院分区：
文献类型：
--
作者：
Graef M;Friedman JR;Graham C;Babu M;Nunnari J
ERES 功能是 Atg1 激酶复合物下游自噬机制组装所必需的，并且与该过程每个阶段自噬体的形成相关。 ERES 是自噬体生物发生的自噬机制的核心组成部分。自噬是所有真核生物中保守的中心稳态和应激反应途径。自噬的标志之一是自噬体的从头形成。这些双膜囊泡结构在液泡/溶酶体周围形成并输送货物以供液泡/溶酶体降解。自噬体在何处以及如何形成是悬而未决的问题。在这里，我们通过蛋白质组学、细胞学和功能分析表明，自噬体在空间、物理和功能上与内质网出口位点 (ERES) 相关，ERES 是内质网的专门区域，其中生成 COPII 转运囊泡。我们的数据表明，ERES 是核心自噬体生物发生组件，其功能是在吞噬细胞组装位点 Atg1 激酶复合物紧下游的自噬机制的分层组装所必需的。
ERES function is required for assembly of the autophagy machinery immediately downstream of the Atg1 kinase complex and is associated with formation of autophagosomes at every stage of the process. ERES are core components of the autophagy machinery for the biogenesis of autophagosomes. Autophagy is a central homeostasis and stress response pathway conserved in all eukaryotes. One hallmark of autophagy is the de novo formation of autophagosomes. These double-membrane vesicular structures form around and deliver cargo for degradation by the vacuole/lysosome. Where and how autophagosomes form are outstanding questions. Here we show, using proteomic, cytological, and functional analyses, that autophagosomes are spatially, physically, and functionally linked to endoplasmic reticulum exit sites (ERES), which are specialized regions of the endoplasmic reticulum where COPII transport vesicles are generated. Our data demonstrate that ERES are core autophagosomal biogenesis components whose function is required for the hierarchical assembly of the autophagy machinery immediately downstream of the Atg1 kinase complex at phagophore assembly sites.