Cell：细胞自噬降解蛋白选择机制

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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。

细胞自噬在进化过程中是一个保守的胞内异化系统，可以大批量的降解蛋白，但是关于自噬系统中选择蛋白的机制却一直鲜为人知。北京生命科学研究所张宏研究小组以秀丽隐杆线虫为模型，在秀丽隐性杆线虫胚胎发生期，将未分化的体细胞中含有来自母体的P颗粒（P granule）的部分蛋白被自体吞噬作用清除掉。这些P颗粒降解的过程中，必须有sepa-1介导，而自体吞噬功能发生变异的个体，P颗粒会蓄积在一起，形成PGL颗粒团。SEPA-1样的蛋白会聚集起来，并且会优先协助自体吞噬作用发生。SEPA-1直接与P颗粒的组份PGL-3结合，还可与自体吞噬蛋白LGG-1/Atg8结合。SEPA-1聚合物始终与PGL-3及LGG-1 puncta结合在一起。最后得出结果，在自体吞噬过程中，SEPA-1在蛋白识别与蛋白降解过程中起桥分子（中间介导）作用。

研究结果表明，自体吞噬作用优先降解蛋白聚合物，尤其是在动物体发育的过程中，选择性自体吞噬倾向于选择具有显著生理学意义的蛋白聚合物。（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.