SEPA-1 Mediates the Specific Recognition and Degradation of P Granule Components by Autophagy in C. elegans

被引：192

作者：

Zhang, Yuxia ^{[1
]}

Yan, Libo ^{[1
,2
,3
]}

Zhou, Zhi ^{[1
]}

Yang, Peiguo ^{[1
]}

Tian, E. ^{[1
]}

Zhang, Kai ^{[4
]}

Zhao, Yu ^{[1
]}

Li, Zhipeng ^{[1
]}

Song, Bing ^{[1
]}

Han, Jinghua ^{[1
]}

Miao, Long ^{[4
]}

Zhang, Hong ^{[1
]}

机构：

[1] Natl Inst Biol Sci, Beijing 102206, Peoples R China

[2] Chinese Acad Med Sci, Grad Program, Beijing 100730, Peoples R China

[3] Peking Union Med Coll, Beijing 100730, Peoples R China

[4] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China

来源：

CELL | 2009年 / 136卷 / 02期

关键词：

CAENORHABDITIS-ELEGANS; GERM GRANULES; MOLECULAR MACHINERY; SELF-DIGESTION; MECHANISMS; MICE; NEURODEGENERATION; PROTEINS; DISEASE; P62;

D O I：

10.1016/j.cell.2008.12.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：308 / 321

页数：14

共 20 条

[11] Autophagy genes are essential for dauer development and life-span extension in C-elegans [J].