title: Pretaporter, a Drosophila protein serving as a ligand for Draper in the phagocytosis of apoptotic cells.
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.
authors.affiliation: Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kuraishi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Kaz
authors.initials: K
authors.lastname: Nagaosa
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Moki
authors.forename: Yu
authors.initials: Y
authors.lastname: Fujita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakayama
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.forename: Akiko
authors.initials: A
authors.lastname: Shiratsuchi
authors.forename: Naoko
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Ueda
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Awasaki
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006434:Hemocytes / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D008856:Microscopy, Fluorescence / Q000379:methods; D008957:Models, Genetic; D009154:Mutation; D010586:Phagocytes / Q000378:metabolism; D010587:Phagocytosis; D017434:Protein Structure, Tertiary
chemical_list: D029721:Drosophila Proteins; D008024:Ligands; D008565:Membrane Proteins; C495322:drpr protein, Drosophila; C546354:prtp protein, Drosophila