Requirement for a Drosophila E3-ubiquitin ligase in phagocytosis of apoptotic cells.
Many cells die by apoptosis during animal development. Apoptotic cells are rapidly removed through phagocytosis by their neighbors or by macrophages. To genetically dissect this process, we performed an in vivo screen for genes required for efficient phagocytosis of apoptotic cells by Drosophila macrophages and identified pallbearer (pall), which encodes an F box protein. F box proteins generally provide substrate specificity to Skp Cullin F box (SCF) complexes, acting as E3 ligases that target phosphorylated proteins to ubiquitylation and degradation via the 26S proteasome. We showed that Pallbearer functions in an SCF-dependent manner and provided direct evidence of a role for ubiquitylation and proteasomal degradation in phagocytosis of apoptotic corpses in vivo. This work might further our understanding of the regulation of apoptotic cell engulfment and thus our understanding of innate immunity as a whole.
Silva
Elizabeth
E
Medical Research Council Cell Biology Unit, MRC Laboratory for Molecular Cell Biology, Anatomy and Developmental Biology Department, University College London, London WC1E 6BT, UK.
Au-Yeung
Hiu Wan
HW
Van Goethem
Emeline
E
Burden
Jemima
J
Franc
Nathalie C
NC
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D010587:Phagocytosis / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism / Q000648:ultrastructure; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex