4.8 Article

The autophagosomal protein LGG-2 acts synergistically with LGG-1 in dauer formation and longevity in C. elegans

Journal

AUTOPHAGY
Volume 6, Issue 5, Pages 622-633

Publisher

TAYLOR & FRANCIS INC
DOI: 10.4161/auto.6.5.12252

Keywords

LC3/Atg8; post-translational modification; dauer; senescence; starvation

Categories

Funding

  1. Agence National de la Recherche
  2. Association pour la Recherche contre le Cancer
  3. Fondation pour la Recherche Medicale
  4. Ministere de l'Education et de la Recherche Technologique
  5. Action de Soutien a la Technologie et la Recherche en Essonne, Conseil de l'Essonne [FR-W2251]

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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.

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