Pretaporter, a Drosophila protein serving as a ligand for Draper in the phagocytosis of apoptotic cells.
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.
Kuraishi
Takayuki
T
Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
Nakagawa
Yukiko
Y
Nagaosa
Kaz
K
Hashimoto
Yumi
Y
Ishimoto
Takashi
T
Moki
Takeshi
T
Fujita
Yu
Y
Nakayama
Hiroshi
H
Dohmae
Naoshi
N
Shiratsuchi
Akiko
A
Yamamoto
Naoko
N
Ueda
Koichi
K
Yamaguchi
Masamitsu
M
Awasaki
Takeshi
T
Nakanishi
Yoshinobu
Y
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
D029721:Drosophila Proteins; D008024:Ligands; D008565:Membrane Proteins; C495322:drpr protein, Drosophila; C546354:prtp protein, Drosophila