LGG-1/GABARAP lipidation is not required for autophagy and development in Caenorhabditis elegans - Archive ouverte HAL
Article Dans Une Revue eLife Année : 2023

LGG-1/GABARAP lipidation is not required for autophagy and development in Caenorhabditis elegans

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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.
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hal-04157249 , version 1 (10-07-2023)

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Romane Leboutet, Céline Largeau, Leonie Müller, Magali Prigent, Grégoire Quinet, et al.. LGG-1/GABARAP lipidation is not required for autophagy and development in Caenorhabditis elegans. eLife, 2023, 12, pp.e85748. ⟨10.7554/eLife.85748⟩. ⟨hal-04157249⟩
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