title: Autophagy genes coordinate with the class II PI/PtdIns 3-kinase PIKI-1 to regulate apoptotic cell clearance in C. elegans.
abstract: Phagocytosis and autophagy are two lysosome-mediated cellular degradation pathways designed to eliminate extracellular and intracellular constituents, respectively. Recent studies suggest that these two processes intersect. Several autophagy proteins have been shown to participate in clearance of apoptotic cells, but whether and how the autophagy pathway is involved is unclear. Here we showed that loss of function mutations in 19 genes acting at overlapping or distinct stages of autophagy caused increased numbers of cell corpses in C. elegans embryos. In contrast, genes that mediate specific clearance of P granules or protein aggregates through autophagy are dispensable for cell corpse removal. We showed that defective autophagy impairs phagosome maturation and that autophagy genes act in parallel to the class II phosphoinositide (PI)/phosphatidylinositol (PtdIns) 3-kinase PIKI-1 to regulate phagosomal PtdIns3P in a similar manner as VPS-34. Our data indicate that autophagy may coordinate with PIKI-1 to promote phagosome maturation, thus ensuring efficient clearance of apoptotic cells.
authors.affiliation: Graduate Program in Chinese Academy of Medical Sciences and Peking Union Medical College; Beijing, China; National Institute of Biological Sciences; Beijing, China.
authors.forename: Shiya
authors.initials: S
authors.lastname: Cheng
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Wu
authors.forename: Qun
authors.initials: Q
authors.lastname: Lu
authors.forename: Jiacong
authors.initials: J
authors.lastname: Yan
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001343:Autophagy / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D058541:Class II Phosphatidylinositol 3-Kinases / Q000502:physiology*; D058546:Class III Phosphatidylinositol 3-Kinases / Q000235:genetics; D030781:Organisms, Genetically Modified; D010588:Phagosomes / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; C000591234:PIKI-1 protein, C elegans; D019869:Phosphatidylinositol 3-Kinases; D058541:Class II Phosphatidylinositol 3-Kinases; D058546:Class III Phosphatidylinositol 3-Kinases
keywords: C. elegans; apoptotic cell clearance; autophagy; phagosome maturation