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1. chinaXiv:201605.01733 [pdf]

Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy

Wu, Fan; Qi, Xin; Zhao, Hong-Yu; Wang, Zheng; Zhang, Hui; Ren, Jin-Qi; Feng, Wei; Hu, Jun-Jie; Zhang, Hong; Watanabe, Yasunori; Fujioka, Yuko; Noda, Nobuo N.; Guo, Xiang-Yang; Fang, Tian-Cheng; Wang, Peng; Shen, Yu-Xian
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology

Multicellular organisms have multiple homologs of the yeast ATG8 gene, but the differential roles of these homologs in autophagy during development remain largely unknown. Here we investigated structure/function relationships in the two C. elegans Atg8 homologs, LGG-1 and LGG-2. lgg-1 is essential for degradation of protein aggregates, while lgg-2 has cargo-specific and developmental-stage-specific roles in aggregate degradation. Crystallography revealed that the N-terminal tails of LGG-1 and LGG-2 adopt the closed and open form, respectively. LGG-1 and LGG-2 interact differentially with autophagy substrates and Atg proteins, many of which carry a LIR motif. LGG-1 and LGG-2 have structurally distinct substrate binding pockets that prefer different residues in the interacting LIR motif, thus influencing binding specificity. Lipidated LGG-1 and LGG-2 possess distinct membrane tethering and fusion activities, which may result from the N-terminal differences. Our study reveals the differential function of two ATG8 homologs in autophagy during C. elegans development.

submitted time 2016-05-15 Hits10580Downloads1352 Comment 0

2. chinaXiv:201605.01461 [pdf]

Guidelines for monitoring autophagy in Caenorhabditis elegans

Zhang, Hong; Guo, Bin; Lin, Long; Lu, Qun; Wu, Fan; Chang, Jessica T.; Hansen, Malene; Kumsta, Caroline; Lapierre, Louis R.; Jia, Kailiang; Kovacs, Attila L.; Legouis, Renaud; Melendez, Alicia; Melendez, Alicia; O'Rourke, Eyleen J.; Sato, Ken; Sato, Miyuki; Wang, Xiaochen
Subjects: Biology >> Biophysics >> Cell Biology

The cellular recycling process of autophagy has been extensively characterized with standard assays in yeast and mammalian cell lines. In multicellular organisms, numerous external and internal factors differentially affect autophagy activity in specific cell types throughout the stages of organismal ontogeny, adding complexity to the analysis of autophagy in these metazoans. Here we summarize currently available assays for monitoring the autophagic process in the nematode C. elegans. A combination of measuring levels of the lipidated Atg8 ortholog LGG-1, degradation of well-characterized autophagic substrates such as germline P granule components and the SQSTM1/p62 ortholog SQST-1, expression of autophagic genes and electron microscopy analysis of autophagic structures are presently the most informative, yet steady-state, approaches available to assess autophagy levels in C. elegans. We also review how altered autophagy activity affects a variety of biological processes in C. elegans such as L1 survival under starvation conditions, dauer formation, aging, and cell death, as well as neuronal cell specification. Taken together, C. elegans is emerging as a powerful model organism to monitor autophagy while evaluating important physiological roles for autophagy in key developmental events as well as during adulthood.

submitted time 2016-05-12 Hits1961Downloads1212 Comment 0

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