Identification of calreticulin as a marker for phagocytosis of apoptotic cells in Drosophila

Takayuki Kuraishi, Junko Manaka, Mari Kono, Hidenari Ishii, Naoko Yamamoto, Keita Koizumi, Akiko Shiratsuchi, Bok Luel Lee, Haruhiro Higashida, Yoshinobu Nakanishi

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61 Citations (Scopus)


Apoptotic cell phagocytosis is initiated through the specific interaction between markers for phagocytosis present at the surface of targets and their receptors of phagocytes. Although many molecules have been proposed to be phagocytosis markers and receptors in mammals, information as to the identity of those molecules is limited for invertebrate animals. Calreticulin, a molecular chaperone that functions in the lumen of the endoplasmic reticulum, was recently reported to be the second general marker, the membrane phospholipid phosphatidylserine being the first, for mammalian apoptotic cells to be recognized by phagocytes. We here asked whether or not calreticulin serves as a marker for phagocytosis in Drosophila. Phagocytosis of apoptotic S2 cells by Drosophila hemocyte-derived l(2)mbn cells, which we previously showed to occur independent of phosphatidylserine, was inhibited by the addition of anti-calreticulin antibody. This inhibition was observed when the target cells, but not phagocytes, were pre-incubated with the antibody. In addition, RNA interference-mediated reduction of calreticulin expression in apoptotic S2 cells, but not in l(2)mbn cells, reduced the level of phagocytosis. An immunocytochemical analysis revealed that calreticulin is widely distributed at the surface of viable S2 cells. After the induction of apoptosis, cell surface calreticulin seemed to form aggregates, with no change in its amount. Furthermore, in embryos of a mutant Drosophila strain that expresses calreticulin at a reduced level, the level of phagocytosis of apoptotic cells was about a half of that observed in embryos of a wild-type strain. These results collectively indicate that calreticulin is the first molecule to be identified as a marker for phagocytosis of apoptotic cells by Drosophila phagocytes.

Original languageEnglish
Pages (from-to)500-510
Number of pages11
JournalExperimental Cell Research
Issue number3
Publication statusPublished - 2007 Feb 1


  • Apoptosis
  • Calreticulin
  • Drosophila
  • Phagocytosis
  • RNAi

ASJC Scopus subject areas

  • Cell Biology


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