LGG-1/GABARAP lipidation is not required for autophagy and development in Caenorhabditis elegans
- Université Paris-Saclay, CEA, CNRS, France
- University of Cologne, Germany
- Laboratoire de Chimie de Coordination (LCC), CNRS, France
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file. Further information and requests for resources and reagents should be directed to the corresponding author, Renaud Legouis (renaud.legouis@i2bc.paris-saclay.fr).
Article and author information
Author details
Funding
Fondation pour la Recherche Médicale (ECO20170637554)
- Romane Leboutet
Agence Nationale de la Recherche (project EAT,ANR-12-BSV2-018)
- Renaud Legouis
Fondation ARC pour la Recherche sur le Cancer (SFI20111203826)
- Renaud Legouis
Ligue Contre le Cancer (M29506)
- Renaud Legouis
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Hong Zhang, Institute of Biophysics, Chinese Academy of Sciences, China
Version history
- Preprint posted: October 5, 2021 (view preprint)
- Received: December 22, 2022
- Accepted: June 30, 2023
- Accepted Manuscript published: July 3, 2023 (version 1)
- Version of Record published: July 12, 2023 (version 2)
Copyright
© 2023, Leboutet et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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LGG-1/GABARAP lipidation is not required for autophagy and development in Caenorhabditis elegans
eLife 12:e85748.
https://doi.org/10.7554/eLife.85748
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