报告题目：C. elegans as a Multicellular Model to Delineate the Autophagy Pathway
报告人： 张宏 , 博士
报告人： 张宏 , 博士
北京生命科学研究所高级研究员
时 间： 2011年5月23日（星期一）下午4点
时 间： 2011年5月23日（星期一）下午4点
地 点： 医学院综合楼205报告厅
Abstract Summary:
Autophagy, an evolutionarily conserved intracellular catabolic process, involves de novo formation of a double membrane structure, called the autophagosome, which engulfs portions of the cytosol and/or damaged organelles and delivers them to lysosomes for degradation. Deregulated autophagy has been linked to a variety of pathological conditions in mammals, including neurodegeneration, cardiomyopathy and tumor progression.
In yeast, genetic screens have identified about 20 Atg genes essential for starvation-induced autophagy. Studies of autophagy in higher eukaryotes are greatly facilitated by the functional conservation of yeast Atg proteins. However, autophagy in higher eukaryotes involves much more complex membrane dynamics. So far, very little is known about higher eukaryote-specific autophagy components. We found that during C. elegans embyogenesis a group of proteins, including components of germline P granules and the p62 homolog, T12G3.1, are selectively removed by autophagy. We performed genetic screens to identify mutants with defective degradation of these autophagy substrates. In addition to yeast ATG gene homologs, we also identified novel genes that did not map to known Atg loci, named epg (ectopic PGL granules) genes. We characterized four novel autophagy genes, epg-2, -3, -4 and -5. epg-2 encodes a coiled-coil protein that functions in specific autophagic cargo recognition. epg-3, -4 and -5 encode proteins that are highly conserved in higher eukaryotes, including mammals, but are absent in yeast. epg-3 encodes the homolog of mammalian vacuole membrane protein 1 (VMP1). epg-4 encodes the homolog of EI24/PIG8, a target of the tumor suppressor protein p53. epg-5 encodes a novel protein whose human homolog is frequently mutated in breast cancers. Mammalian homologs of EPG-3/VMP1, EPG-4/EI24 and EPG-5/mEPG5 are essential for starvation-induced autophagy. Our study establishes C. elegans as a multicellular genetic model to delineate the autophagy pathway and provides mechanistic insights into metazoan-specific autophagic process.
Selected Publications
1. Huang, X.X., Zhang, H. and Zhang, H. (2011) The zinc-finger protein SEA-2 regulates larval developmental timing and adult life span in C. elegans. Development 138, 2059-2068.
2. Yang, P.G. and Zhang, H. (2011) The coiled-coil domain protein EPG-8 plays an essential role in the autophagy pathway in C. elegans. Autophagy 7, 159-165.
3. Tian, Y., Li, Z.P., Hu, W.Q., Ren, H.Y., Tian, E, Zhao, Y., Lu, Q., Huang, X.X., Yang, P.G., Li, X., Wang, X.C., Kovács, A.L., Yu, L. and Zhang, H. (2010) C. elegans screen identifies autophagy genes specific to multicellular organisms. Cell 141, 1042-1055.
4. Tian, E, Wang, F.X., Han, J.H., and Zhang, H. (2009) epg-1 functions in autophagy-regulated processes and may encode a highly divergent Atg13 homolog in C. elegans. Autophagy 5, 608-615.
5. Zhang, Y.X., Yan, L.B., Zhou, Z., Yang, P.G., Tian E, Zhang, K., Zhao, Y., Li, Z.P., Song, B., Han, J.H., Miao, L., and Zhang, H. (2009) SEPA-1 mediates the specific recognition and degradation of P granule components by autophagy in C. elegans. Cell 136, 308-321.
6. Cai, Q.C., Sun, Y.Y., Huang, X.X., Guo, C., Zhang, Y.X., Zhu, Z.Y., and Zhang, H. (2008) The Caenorhabditis elegans PcG-like gene sop-2 regulates the temporal and sexual specificities of cell fates. Genetics 178, 1445-1456.
7. Yang, Y., Sun, Y.Y., Luo, X., Zhang, Y.X., Chen, Y.Y., Tian, E, Lints, R., and Zhang, H. (2007) Polycomb-like genes are necessary for specification of dopaminergic and serotonergic neurons in Caenorhabditis elegans. PNAS 104, 852-857.
