2009年1月23日，北京生命科学研究所（NIBS）张宏实验室在Cell杂志上以Featured Article形式发表题为“SEPA-1 Mediates the Specific Recognition and Degradation of P Granule Components by Autophagy in C. elegans”的文章。该文章报道了在线虫自体吞噬（autophagy）过程中，体细胞中P颗粒组分的特异性识别和降解是由SEPA-1介导的。
细胞自噬（autophagy）是广泛存在于真核细胞内的一种溶酶体依赖性的降解途径，在饥饿的条件下，它可以调节细胞内长寿命蛋白和细胞器的降解，降解产物再被细胞重新利用。因此自噬在细胞发育、细胞免疫、组织重塑及对环境适应等方面有着十分重要的作用。
自体吞噬在进化过程中是一个保守的胞内异化系统，可以大批量的降解胞内蛋白，但是有关自体吞噬系统中选择蛋白的机制却一直鲜为人知。张宏实验室研究人员以线虫为模型，证明在线虫的胚胎时期，未分化的体细胞中含有的来自母体的P颗粒（P granule）的部分蛋白是由自体吞噬作用清除掉的，在自体吞噬相关基因突变的线虫体细胞内，P颗粒会聚集形成PGL颗粒团（PGL granules），随后又进一步证明这种P颗粒团的降解是由SEPA-1介导完成的，SEPA-1一方面直接与P颗粒组分PGL-3结合，另一方面还直接结合自体吞噬相关蛋白LGG-1/Atg-8，因此，SEPA-1在蛋白识别与降解过程中起桥梁作用。该研究表明自体吞噬在蛋白降解中的相关机制，强调了选择性自体吞噬作用在动物发育过程中的生理意义。同期Cell杂志专门为该文发表了一篇题为“Autophagy SEPArates Germline and Somatic Cells”的评述文章。
张玉霞，严立波，周智和杨培国为该文章共同第一作者，论文的其他作者还有本所的田娥，赵玉，李志鹏，宋冰，韩敬华和中国科学院生物物理所的张凯和苗龙博士。张宏博士为本文的通讯作者，项研究由科技部863项目资助，在北京生命科学研究所完成。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
