RRC ID 45756
Author Jenzer C, Manil-Ségalen M, Lefebvre C, Largeau C, Glatigny A, Legouis R.
Title Human GABARAP can restore autophagosome biogenesis in a C. elegans lgg-1 mutant.
Journal Autophagy
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.
Volume 10(10)
Pages 1868-72
Published 2014-10-1
DOI 10.4161/auto.29745
PII 29745
PMID 25126728
PMC PMC4198372
MeSH Adaptor Proteins, Signal Transducing / metabolism* Animals Autophagy* Caenorhabditis elegans / cytology* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics* Endosomes / metabolism Genetic Complementation Test Green Fluorescent Proteins / metabolism Humans Lysosomes / metabolism Microtubule-Associated Proteins / genetics* Microtubule-Associated Proteins / metabolism* Mutation / genetics* Phagosomes / metabolism*
IF 9.77
Times Cited 7
C.elegans tm5755 tm3489