RRC ID 59359
Author Jenzer C, Simionato E, Largeau C, Scarcelli V, Lefebvre C, Legouis R.
Title Autophagy mediates phosphatidylserine exposure and phagosome degradation during apoptosis through specific functions of GABARAP/LGG-1 and LC3/LGG-2.
Journal Autophagy
Abstract Phagocytosis and macroautophagy/autophagy are 2 processes involved in lysosome-mediated clearance of extracellular and intracellular components, respectively. Recent studies have identified the recruitment of the autophagic protein LC3 during phagocytosis of apoptotic corpses in what is now called LC3-associated phagocytosis (LAP). LAP is a distinct process from autophagy but it relies on some members of the autophagy pathway to allow efficient degradation of the phagocytosed cargo. We investigated whether both LC3/LGG-2 and GABARAP/LGG-1 are involved in phagocytosis of apoptotic corpses during embryonic development of Caenorhabditis elegans. We discovered that both LGG-1 and LGG-2 are involved in the correct elimination of apoptotic corpses, but that they have different functions. lgg-1 and lgg-2 mutants present a delay in phagocytosis of apoptotic cells but genetic analyses indicate that LGG-1 and LGG-2 act upstream and downstream of the engulfment pathways, respectively. Moreover, LGG-1 and LGG-2 display different cellular localizations with enrichment in apoptotic corpses and phagocytic cells, respectively. For both LGG-1 and LGG-2, subcellular localization is vesicular and dependent on UNC-51/ULK1, BEC-1/BECN1 and the lipidation machinery, indicating that their functions during phagocytosis of apoptotic corpses mainly rely on autophagy. Finally, we show that LGG-1 is involved in the exposure of the 'eat-me signal' phosphatidylserine at the surface of the apoptotic cell to allow its recognition by the phagocytic cell, whereas LGG-2 is involved in later steps of phagocytosis to allow efficient cell corpse clearance by mediating the maturation/degradation of the phagosome.
Volume 15(2)
Pages 228-241
Published 2019-2-1
DOI 10.1080/15548627.2018.1512452
PMID 30160610
PMC PMC6333449
MeSH Animals Apoptosis* Autophagy* Caenorhabditis elegans / cytology* Caenorhabditis elegans / embryology Caenorhabditis elegans / metabolism* Caenorhabditis elegans / ultrastructure Caenorhabditis elegans Proteins / metabolism* Lysosomes / metabolism Membrane Fusion Microtubule-Associated Proteins / metabolism* Models, Biological Phagocytosis Phagosomes / metabolism* Phagosomes / ultrastructure Phosphatidylserines / metabolism*
IF 11.059
Times Cited 6
C.elegans tm3489 tm5755 tm2423 tm847 tm2253