title: Autophagy genes function sequentially to promote apoptotic cell corpse degradation in the engulfing cell.
abstract: Apoptotic cell degradation is a fundamental process for organism development, and impaired clearance causes inflammatory or autoimmune disease. Although autophagy genes were reported to be essential for exposing the engulfment signal on apoptotic cells, their roles in phagocytes for apoptotic cell removal are not well understood. In this paper, we develop live-cell imaging techniques to study apoptotic cell clearance in the Caenorhabditis elegans Q neuroblast lineage. We show that the autophagy proteins LGG-1/LC3, ATG-18, and EPG-5 were sequentially recruited to internalized apoptotic Q cells in the phagocyte. In atg-18 or epg-5 mutants, apoptotic Q cells were internalized but not properly degraded; this phenotype was fully rescued by the expression of autophagy genes in the phagocyte. Time-lapse analysis of autophagy mutants revealed that recruitment of the small guanosine triphosphatases RAB-5 and RAB-7 to the phagosome and the formation of phagolysosome were all significantly delayed. Thus, autophagy genes act within the phagocyte to promote apoptotic cell degradation.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.forename: Yihong
authors.initials: Y
authors.lastname: Yang
authors.forename: Yongping
authors.initials: Y
authors.lastname: Chai
authors.forename: Baohui
authors.initials: B
authors.lastname: Chen
authors.forename: Shiya
authors.initials: S
authors.lastname: Cheng
authors.forename: Dong
authors.initials: D
authors.lastname: Tian
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Wang
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Vale
authors.forename: Guangshuo
authors.initials: G
authors.lastname: Ou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001343:Autophagy / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D008247:Lysosomes / Q000378:metabolism; D009154:Mutation; D010586:Phagocytes / Q000166:cytology / Q000378:metabolism*; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism; D010641:Phenotype; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; C553666:LGL-1 protein, C elegans; C558452:Rab-5 protein, C elegans; D033921:Vesicular Transport Proteins