2009年1月23日，北京生命科學(xué)研究所（NIBS）張宏實驗室在Cell雜志上以Featured Article形式發(fā)表題為“SEPA-1 Mediates the Specific Recognition and Degradation of P Granule Components by Autophagy in C. elegans”的文章,。該文章報道了在線蟲自體吞噬（autophagy）過程中，體細胞中P顆粒組分的特異性識別和降解是由SEPA-1介導(dǎo)的,。
細胞自噬（autophagy）是廣泛存在于真核細胞內(nèi)的一種溶酶體依賴性的降解途徑,，在饑餓的條件下,，它可以調(diào)節(jié)細胞內(nèi)長壽命蛋白和細胞器的降解，降解產(chǎn)物再被細胞重新利用,。因此自噬在細胞發(fā)育,、細胞免疫、組織重塑及對環(huán)境適應(yīng)等方面有著十分重要的作用,。
自體吞噬在進化過程中是一個保守的胞內(nèi)異化系統(tǒng),，可以大批量的降解胞內(nèi)蛋白，但是有關(guān)自體吞噬系統(tǒng)中選擇蛋白的機制卻一直鮮為人知,。張宏實驗室研究人員以線蟲為模型,，證明在線蟲的胚胎時期，未分化的體細胞中含有的來自母體的P顆粒（P granule）的部分蛋白是由自體吞噬作用清除掉的,，在自體吞噬相關(guān)基因突變的線蟲體細胞內(nèi),，P顆粒會聚集形成PGL顆粒團（PGL granules），隨后又進一步證明這種P顆粒團的降解是由SEPA-1介導(dǎo)完成的,，SEPA-1一方面直接與P顆粒組分PGL-3結(jié)合,，另一方面還直接結(jié)合自體吞噬相關(guān)蛋白LGG-1/Atg-8，因此,，SEPA-1在蛋白識別與降解過程中起橋梁作用,。該研究表明自體吞噬在蛋白降解中的相關(guān)機制，強調(diào)了選擇性自體吞噬作用在動物發(fā)育過程中的生理意義,。同期Cell雜志專門為該文發(fā)表了一篇題為“Autophagy SEPArates Germline and Somatic Cells”的評述文章,。
張玉霞，嚴立波,，周智和楊培國為該文章共同第一作者,，論文的其他作者還有本所的田娥，趙玉,，李志鵬,，宋冰，韓敬華和中國科學(xué)院生物物理所的張凱和苗龍博士,。張宏博士為本文的通訊作者,，項研究由科技部863項目資助，在北京生命科學(xué)研究所完成,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell, 23 January 2009,doi:10.1016/j.cell.2008.12.022
SEPA-1 Mediates the Specific Recognition and Degradation of P Granule Components by Autophagy in C. elegans
Yuxia Zhang1,4,Libo Yan1,2,4,Zhi Zhou1,4,Peiguo Yang1,4,E. Tian1,Kai Zhang3,Yu Zhao1,Zhipeng Li1,Bing Song1,Jinghua Han1,Long Miao3andHong Zhang1,,
1 National Institute of Biological Sciences, Beijing 102206, P.R. China
2 Graduate Program in Chinese Academy of Medical Sciences and Peking union Medical College, Beijing 100730, P.R. China
3 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China
4 These authors contributed equally to this work
Summary
How autophagy, an evolutionarily conserved intracellular catabolic system for bulk degradation, selectively degrades protein aggregates is poorly understood. Here, we show that several maternally derived germ P granule components are selectively eliminated by autophagy in somatic cells during C. elegans embryogenesis. The activity of sepa-1 is required for the degradation of these P granule components and for their accumulation into aggregates, termed PGL granules, in autophagy mutants. SEPA-1 forms protein aggregates and is also a preferential target of autophagy. SEPA-1 directly binds to the P granule component PGL-3 and also to the autophagy protein LGG-1/Atg8. SEPA-1 aggregates consistently colocalize with PGL granules and with LGG-1 puncta. Thus, SEPA-1 functions as a bridging molecule in mediating the specific recognition and degradation of P granule components by autophagy. Our study reveals a mechanism for preferential degradation of protein aggregates by autophagy and emphasizes the physiological significance of selective autophagy during animal development.
