The autophagosomal protein LGG-2 acts synergistically with LGG-1 in dauer formation and longevity in C. elegans.
Autophagy has an important function in degrading cytoplasmic components to maintain cellular homeostasis, but is also required during development. The formation of the autophagic vesicles requires the recruitment of the Atg8 ubiquitin-like proteins to the membrane of the nascent autophagosomes. Atg8 is a highly conserved gene which has been duplicated during metazoan evolution.  In this report we have investigated, in the nematode C. elegans, the functions and localizations of the two Atg8p homologues LGG-2 and LGG-1. Phylogenetic analyses suggest that LGG-2 is more closely related to the human protein LC3 than LGG-1. LGG-1 but not LGG-2 is able to functionally complement the atg8 mutant yeast. The C-terminal glycine residue of LGG-2 is essential for post-translational modification and localization to the autophagosomes. During C. elegans development the two proteins share a similar expression pattern and localization but LGG-2 is more abundant in the neurons. Using genetic tools to either reduce or increase the autophagic flux we show that both LGG-2 and LGG-1 are addressed to the autophagosomal/lysosomal degradative system. We also demonstrate that the localization of both proteins is modified in several physiological processes when autophagy is induced, namely during diapause "dauer" larval formation, starvation and aging. Finally, we demonstrate that both LGG-2 and LGG-1 act synergistically and are involved in dauer formation and longevity of the worm.
Alberti
Adriana
A
Centre de Génétique Moléculaire, CNRS FRE3144, Université Paris Sud, Gif-sur-Yvette, France.
Michelet
Xavier
X
Djeddi
Abderazak
A
Legouis
Renaud
R
D000595:Amino Acid Sequence; D000818:Animals; D001343:Autophagy / Q000235:genetics; D000071190:Autophagy-Related Protein 8 Family; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth / Q000235:genetics; D016678:Genome / Q000235:genetics; D005998:Glycine / Q000378:metabolism; D006801:Humans; D007814:Larva / Q000502:physiology; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008247:Lysosomes / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010588:Phagosomes / Q000378:metabolism*; D021381:Protein Transport; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
C113757:ATG8 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; D029742:Caenorhabditis elegans Proteins; D008869:Microtubule-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; D005998:Glycine