Pretaporter, a Drosophila protein serving as a ligand for Draper in the phagocytosis of apoptotic cells

Takayuki Kuraishi, Yukiko Nakagawa, Kaz Nagaosa, Yumi Hashimoto, Takashi Ishimoto, Takeshi Moki, Yu Fujita, Hiroshi Nakayama, Naoshi Dohmae, Akiko Shiratsuchi, Naoko Yamamoto, Koichi Ueda, Masamitsu Yamaguchi, Takeshi Awasaki, Yoshinobu Nakanishi

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3868-3878
Number of pages11
JournalEMBO Journal
Volume28
Issue number24
DOIs
Publication statusPublished - 2009 Dec

Keywords

  • Apoptosis
  • Drosophila
  • Endoplasmic reticulum
  • Phagocytosis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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