2012年8月19日,,北京生命科學研究所張宏實驗室在Autophagy雜志上在線發(fā)表題為“The C. elegans ATG101 homolog EPG-9 directly interacts with EPG-1/Atg13 and is essential for autophagy”的文章,。該文章報道了線蟲中的EPG-9與EPG-1形成復合體,在細胞自噬過程中起作用,。
自噬是一個進化上保守的過程, 它包括將細胞質成分包裹在一個稱為自噬體的雙層膜結構,以及運送至溶酶體進行降解的過程。通過在酵母中進行遺傳篩選,已有多個對于自噬小體形成起重要作用的自噬相關基因被發(fā)現。這篇文章中,我們分離得到了一個新的自噬基因,,epg-9, 該基因的缺失導致自噬降解過程出現問題,從而在線蟲的卵發(fā)育過程中累積大量蛋白聚集體,。epg-9 的突變降低了在饑餓條件下線蟲的存活率,。epg-9 的突變體呈現 unc-51/Atg1 或epg-1/Atg13 功能缺失的典型特征。epg-9 編碼的蛋白與哺乳動物的ATG101 具有高度同源性,。EPG-9 直接與EPG-1/Atg13相互作用,。我們的研究表明線蟲中EPG-9與EPG-1形成復合體,在細胞自噬過程中起作用。
北京生命科學研究所博士研究生梁倩倩為文章的第一作者,,論文的其它作者包括楊培國博士,,田娥博士以及生物信息中心韓敬華老師。張宏博士為本文的通訊作者,,該項研究由國家基礎研究基金973資助,,張宏博士的研究獲得HHMI國際青年科學家獎支持,在北京生命科學研究所完成,。(生物谷Bioon.com)
doi:10.4161/auto.21163
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The C. elegans ATG101 homolog EPG-9 directly interacts with EPG-1/Atg13 and is essential for autophagy
Qianqian Liang, Peiguo Yang, E Tian, Jinghua Han and Hong Zhang
Autophagy is an evolutionarily conserved catabolic process that involves the engulfment of cytoplasmic contents in a closed double-membrane structure, called the autophagosome, and their subsequent delivery to the vacuole/lysosomes for degradation. Genetic screens in Saccharomyces cerevisiae have identified more than 30 autophagy-related (Atg) genes that are essential for autophagosome formation. Here we isolated a novel autophagy gene, epg-9, whose loss of function causes defective autophagic degradation of a variety of protein aggregates during C. elegans embryogenesis. Mutations in epg-9 also reduce survival of animals under food depletion conditions. epg-9 mutants exhibit autophagy phenotypes characteristic of those associated with loss of function of unc-51/Atg1 and epg-1/Atg13. epg-9 encodes a protein with significant homology to mammalian ATG101. EPG-9 directly interacts with EPG-1/Atg13. Our study indicates that EPG-9 forms a complex with EPG-1 in the aggrephagy pathway in C. elegans.