title: Human GABARAP can restore autophagosome biogenesis in a C. elegans lgg-1 mutant.
abstract: We recently described in C. elegans embryos, the acquisition of specialized functions for orthologs of yeast Atg8 (e.g., mammalian MAP1LC3/LC3) in allophagy, a selective and developmentally regulated autophagic process. During the formation of double-membrane autophagosomes, the ubiquitin-like Atg8/LC3 proteins are recruited to the membrane through a lipidation process. While at least 6 orthologs and paralogs are present in mammals, C. elegans only possesses 2 orthologs, LGG-1 and LGG-2, corresponding to the GABARAP-GABARAPL2/GATE-16 and the MAP1LC3 families, respectively. During allophagy, LGG-1 acts upstream of LGG-2 and is essential for autophagosome biogenesis, whereas LGG-2 facilitates their maturation. We demonstrated that LGG-2 directly interacts with the HOPS complex subunit VPS-39, and mediates the tethering between autophagosomes and lysosomes, which also requires RAB-7. In the present addendum, we compared the localization of autophagosomes, endosomes, amphisomes, and lysosomes in vps-39, rab-7, and lgg-2 depleted embryos. Our results suggest that lysosomes interact with autophagosomes or endosomes through a similar mechanism. We also performed a functional complementation of an lgg-1 null mutant with human GABARAP, its closer homolog, and showed that it localizes to autophagosomes and can rescue LGG-1 functions in the early embryo.
authors.affiliation: Centre de Génétique Moléculaire; CNRS UPR3404;Université Paris Sud; Gif-sur-Yvette, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Jenzer
authors.affiliation: Centre de Génétique Moléculaire; CNRS UPR3404;Université Paris Sud; Gif-sur-Yvette, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Manil-Ségalen
authors.affiliation: Centre de Génétique Moléculaire; CNRS UPR3404;Université Paris Sud; Gif-sur-Yvette, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Lefebvre
authors.affiliation: Centre de Génétique Moléculaire; CNRS UPR3404;Université Paris Sud; Gif-sur-Yvette, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Largeau
authors.affiliation: Centre de Génétique Moléculaire; CNRS UPR3404;Université Paris Sud; Gif-sur-Yvette, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Glatigny
authors.affiliation: Centre de Génétique Moléculaire; CNRS UPR3404;Université Paris Sud; Gif-sur-Yvette, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Legouis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D011992:Endosomes / Q000378:metabolism; D005816:Genetic Complementation Test; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D010588:Phagosomes / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; C116741:GABARAP protein, human; C587195:LGG-1 protein, C elegans; D008869:Microtubule-Associated Proteins; D049452:Green Fluorescent Proteins
keywords: C. elegans; GABARAP; LC3; allophagy; atg8; embryo