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PMID:19927123

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Citation

Kuraishi, T, Nakagawa, Y, Nagaosa, K, Hashimoto, Y, Ishimoto, T, Moki, T, Fujita, Y, Nakayama, H, Dohmae, N, Shiratsuchi, A, Yamamoto, N, Ueda, K, Yamaguchi, M, Awasaki, T and Nakanishi, Y (2009) Pretaporter, a Drosophila protein serving as a ligand for Draper in the phagocytosis of apoptotic cells. EMBO J. 28:3868-78

Abstract

Phagocytic removal of cells undergoing apoptosis is necessary for animal development and tissue homeostasis. Draper, a homologue of the Caenorhabditis elegans phagocytosis receptor CED-1, is responsible for the phagocytosis of apoptotic cells in Drosophila, but its ligand presumably present on apoptotic cells remains unknown. An endoplasmic reticulum protein that binds to the extracellular region of Draper was isolated. Loss of this protein, which we name Pretaporter, led to a reduced level of apoptotic cell clearance in embryos, and the overexpression of pretaporter in the mutant flies rescued this defect. Results from genetic analyses suggested that Pretaporter functionally interacts with Draper and the corresponding signal mediators. Pretaporter was exposed at the cell surface after the induction of apoptosis, and cells artificially expressing Pretaporter at their surface became susceptible to Draper-mediated phagocytosis. Finally, the incubation with Pretaporter augmented the tyrosine-phosphorylation of Draper in phagocytic cells. These results collectively suggest that Pretaporter relocates from the endoplasmic reticulum to the cell surface during apoptosis to serve as a ligand for Draper in the phagocytosis of apoptotic cells.

Links

PubMed PMC2797060 Online version:10.1038/emboj.2009.343

Keywords

Animals; Apoptosis; Cell Membrane/metabolism; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila Proteins/physiology; Drosophila melanogaster/genetics; Drosophila melanogaster/metabolism; Endoplasmic Reticulum/metabolism; Hemocytes/metabolism; Ligands; Membrane Proteins/genetics; Membrane Proteins/physiology; Microscopy, Fluorescence/methods; Models, Genetic; Mutation; Phagocytes/metabolism; Phagocytosis; Protein Structure, Tertiary

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:TXND5

located_in

GO:0005783: endoplasmic reticulum

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:TXND5

involved_in

GO:0043277: apoptotic cell clearance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:TXND5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9W0A0

F

Seeded From UniProt

complete

DROME:DRPR

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9VYV3

F

Seeded From UniProt

complete


See also

References

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