2012年8月19日,北京生命科學(xué)研究所張宏實(shí)驗(yàn)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(bào)道了線蟲(chóng)中的EPG-9與EPG-1形成復(fù)合體,在細(xì)胞自噬過(guò)程中起作用。
自噬是一個(gè)進(jìn)化上保守的過(guò)程, 它包括將細(xì)胞質(zhì)成分包裹在一個(gè)稱(chēng)為自噬體的雙層膜結(jié)構(gòu),以及運(yùn)送至溶酶體進(jìn)行降解的過(guò)程,。通過(guò)在酵母中進(jìn)行遺傳篩選,已有多個(gè)對(duì)于自噬小體形成起重要作用的自噬相關(guān)基因被發(fā)現(xiàn),。這篇文章中,我們分離得到了一個(gè)新的自噬基因,,epg-9, 該基因的缺失導(dǎo)致自噬降解過(guò)程出現(xiàn)問(wèn)題,,從而在線蟲(chóng)的卵發(fā)育過(guò)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(chóng)的存活率,。epg-9 的突變體呈現(xiàn) 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(dòng)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(chóng)中EPG-9與EPG-1形成復(fù)合體,在細(xì)胞自噬過(guò)程中起作用,。
北京生命科學(xué)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(guó)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(xiàng)研究由國(guó)家基礎(chǔ)研究基金973資助,,張宏博士的研究獲得HHMI國(guó)際青年科學(xué)家獎(jiǎng)支持,在北京生命科學(xué)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.