SEPA-1 Mediates the Specific Recognition and Degradation of P Granule Components by Autophagy in C. elegans
SEPA-1 Mediates the Specific Recognition and Degradation of P Granule Components by Autophagy in C. elegans
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DOI：
10.1016/j.cell.2008.12.022
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发表时间：
2009-01-23
期刊：
影响因子：
64.5
通讯作者：
Zhang, Hong
中科院分区：
文献类型：
--
作者：
Zhang, Yuxia;Yan, Libo;Zhang, Hong
自噬是一种进化上保守的细胞内分解代谢系统，用于大量降解，如何选择性地降解蛋白质聚集体还知之甚少。在这里，我们表明，几个母体来源的胚芽P颗粒成分被选择性消除自噬体细胞在C。线虫胚胎发生在自噬突变体中，sepa-1的活性是降解这些P颗粒组分和将其积累成聚集体（称为PGL颗粒）所必需的。SEPA-1形成蛋白质聚集体，也是自噬的优先靶点。SEPA-1直接与P颗粒组分PGL-3结合，还与自噬蛋白LGG-1/Atg 8结合。SEPA-1聚集体始终与PGL颗粒和LGG-1斑点共定位。因此，SEPA-1的功能作为一个桥梁分子介导的特异性识别和降解的P颗粒成分的自噬。我们的研究揭示了自噬优先降解蛋白质聚集体的机制，并强调了选择性自噬在动物发育过程中的生理意义。
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.