RRC ID 80841
Author Leboutet R, Largeau C, Müller L, Prigent M, Quinet G, Rodriguez MS, Cuif MH, Hoppe T, Culetto E, Lefebvre C, Legouis R.
Title LGG-1/GABARAP lipidation is not required for autophagy and development in Caenorhabditis elegans.
Journal Elife
Abstract The ubiquitin-like proteins Atg8/LC3/GABARAP are required for multiple steps of autophagy, such as initiation, cargo recognition and engulfment, vesicle closure and degradation. Most of LC3/GABARAP functions are considered dependent on their post-translational modifications and their association with the autophagosome membrane through a conjugation to a lipid, the phosphatidyl-ethanolamine. Contrarily to mammals, C. elegans possesses single homologs of LC3 and GABARAP families, named LGG-2 and LGG-1. Using site-directed mutagenesis, we inhibited the conjugation of LGG-1 to the autophagosome membrane and generated mutants that express only cytosolic forms, either the precursor or the cleaved protein. LGG-1 is an essential gene for autophagy and development in C. elegans, but we discovered that its functions could be fully achieved independently of its localization to the membrane. This study reveals an essential role for the cleaved form of LGG-1 in autophagy but also in an autophagy-independent embryonic function. Our data question the use of lipidated GABARAP/LC3 as the main marker of autophagic flux and highlight the high plasticity of autophagy.
Volume 12
Published 2023-7-3
DOI 10.7554/eLife.85748
PII 85748
PMID 37395461
PMC PMC10338037
MeSH Animals Apoptosis Regulatory Proteins / metabolism Autophagosomes / metabolism Autophagy Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Humans Mammals / metabolism Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / metabolism Phagocytosis
Resource
C.elegans tm3489 tm5755