title: The C. elegans LC3 acts downstream of GABARAP to degrade autophagosomes by interacting with the HOPS subunit VPS39.
abstract: The formation of the autophagic vesicles requires the recruitment of ubiquitin-like Atg8 proteins to the membrane of nascent autophagosomes. Seven Atg8 homologs are present in mammals, split into the LC3 and the GABARAP/GATE-16 families, whose respective functions are unknown. Using Caenorhabditis elegans, we investigated the functions of the GABARAP and the LC3 homologs, LGG-1 and LGG-2, in autophagosome biogenesis. Both LGG-1 and LGG-2 localize to the autophagosomes but display partially overlapping patterns. During allophagy, a developmentally stereotyped autophagic flux, LGG-1 acts upstream of LGG-2 to allow its localization to autophagosomes. LGG-2 controls the maturation of LGG-1-positive autophagosomes and facilitates the tethering with the lysosomes through a direct interaction with the VPS-39 HOPS complex subunit. Genetic analyses sustain a sequential implication of LGG-1, LGG-2, RAB-7, and HOPS complex to generate autolysosomes. The duplications of Atg8 in metazoans thus allowed the acquisition of specialized functions for autophagosome maturation.
authors.affiliation: Centre de Génétique Moléculaire, CNRS UPR3404 associée à l'Université Paris Sud, Avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Manil-Ségalen
authors.affiliation: Centre de Génétique Moléculaire, CNRS UPR3404 associée à l'Université Paris Sud, Avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Lefebvre
authors.affiliation: Centre de Génétique Moléculaire, CNRS UPR3404 associée à l'Université Paris Sud, Avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Jenzer
authors.affiliation: Institut des Sciences du Végetal, CNRS UPR2355, Avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France; Imagif FRC 3115, Avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Trichet
authors.affiliation: Imagif FRC 3115, Avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Boulogne
authors.affiliation: Institut des Sciences du Végetal, CNRS UPR2355, Avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France; Imagif FRC 3115, Avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Satiat-Jeunemaitre
authors.affiliation: Centre de Génétique Moléculaire, CNRS UPR3404 associée à l'Université Paris Sud, Avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France. Electronic address: renaud.legouis@cgm.cnrs-gif.fr.
authors.forename: Renaud
authors.initials: R
authors.lastname: Legouis
mesh_terms: D000818:Animals; D001343:Autophagy; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C587195:LGG-1 protein, C elegans; C587196:LGG-2 protein, C elegans; D008869:Microtubule-Associated Proteins; D021122:Protein Subunits; D033921:Vesicular Transport Proteins; C587197:vps-39 protein, C elegans