title: Defective Phagocytic Corpse Processing Results in Neurodegeneration and Can Be Rescued by TORC1 Activation.
abstract: The removal of apoptotic cell corpses is important for maintaining homeostasis. Previously, defects in apoptotic cell clearance have been linked to neurodegeneration. However, the mechanisms underlying this are still poorly understood. In this study, we report that the absence of the phagocytic receptor Draper in glia leads to a pronounced accumulation of apoptotic neurons in the brain of Drosophila melanogaster. These dead cells persist in the brain throughout the lifespan of the organism and are associated with age-dependent neurodegeneration. Our data indicate that corpses persist because of defective phagosome maturation, rather than recognition defects. TORC1 activation, or inhibition of Atg1, in glia is sufficient to rescue corpse accumulation as well as neurodegeneration. These results suggest that phagocytosis of apoptotic neurons by glia during development is essential for brain homeostasis in adult flies. Furthermore, it suggests that TORC1 regulates Draper-mediated phagosome maturation.
  
  
  CONCLUSIONS
  Previously, defects in dead cell clearance were linked to neurodegeneration, but the exact mechanisms are not well understood. In this study, we report that the absence of an engulfment receptor leads to a pronounced accumulation of dead neurons in the brain of the fruit fly Drosophila melanogaster. These dead cells persist in the brain throughout the lifespan of the organism and are associated with age-dependent neurodegeneration. Our data indicate that corpses persist because of defective degradation of cells rather than recognition of dead cells.
authors.affiliation: Department of Biology, Boston University, Boston, Massachusetts 02215 and.
authors.forename: Jon Iker
authors.initials: JI
authors.lastname: Etchegaray
authors.affiliation: Department of Biology, Boston University, Boston, Massachusetts 02215 and.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Elguero
authors.affiliation: Department of Biology, Boston University, Boston, Massachusetts 02215 and.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Tran
authors.affiliation: Department of Biology, Boston University, Boston, Massachusetts 02215 and.
authors.forename: Vincent
authors.initials: V
authors.lastname: Sinatra
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: Mel B
authors.initials: MB
authors.lastname: Feany
authors.affiliation: Department of Biology, Boston University, Boston, Massachusetts 02215 and kmccall@bu.edu.
authors.forename: Kimberly
authors.identifier: http://orcid.org/0000-0002-9942-2355
authors.initials: K
authors.lastname: McCall
mesh_terms: D000367:Age Factors; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000473:pathology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D004625:Embryo, Nonmammalian; D039642:Eukaryotic Initiation Factors / Q000172:deficiency / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D007814:Larva; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics* / Q000473:pathology; D009457:Neuroglia / Q000473:pathology* / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D010587:Phagocytosis / Q000502:physiology*; D034622:RNA Interference / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C553179:DRR-2 protein, C elegans; D029721:Drosophila Proteins; D039642:Eukaryotic Initiation Factors; C557617:GAL4 protein, Drosophila; D008565:Membrane Proteins; C570998:TORC1 protein complex, Drosophila; D014157:Transcription Factors; C495322:drpr protein, Drosophila
keywords: Drosophila; autophagy; cell death; glia; neurodegeneration; phagocytosis