Phosphatidylserine recognition and induction of apoptotic cell clearance by Drosophila engulfment receptor Draper

• Published in: Journal of biochemistry (Tokyo) Vol. 153; no. 5; pp. 483 - 491
• Main Authors: Tung, Tran Thanh, Nagaosa, Kaz, Fujita, Yu, Kita, Asana, Mori, Hiroki, Okada, Ryo, Nonaka, Saori, Nakanishi, Yoshinobu
• Format: Journal Article
• Language: English
• Published: England 01-05-2013
• Subjects: Acyltransferases; Animals; Apoptosis - genetics; Apoptosis - physiology; Drosophila; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Nematoda; Phagocytosis - genetics; Phagocytosis - physiology; Phosphatidylserines - metabolism
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/jb/mvt014

The membrane phospholipid phosphatidylserine is exposed on the cell surface during apoptosis and acts as an eat-me signal in the phagocytosis of apoptotic cells in mammals and nematodes. However, whether this is also true in insects was unclear. When milk fat globule-epidermal growth factor 8, a phosphatidylserine-binding protein of mammals, was ectopically expressed in Drosophila, the level of phagocytosis was reduced, whereas this was not the case for the same protein lacking a domain responsible for the binding to phosphatidylserine. We found that the extracellular region of Draper, an engulfment receptor of Drosophila, binds to phosphatidylserine in an enzyme-linked immunosorbent assay-like solid-phase assay and in an assay for surface plasmon resonance. A portion of Draper containing domains EMI and NIM located close to the N-terminus was required for binding to phosphatidylserine, and a Draper protein lacking this region was not active in Drosophila. Finally, the level of tyrosine-phosphorylated Draper, indicative of the activation of Draper, in a hemocyte-derived cell line was increased after treatment with phosphatidylserine-containing liposome. These results indicated that phosphatidylserine serves as an eat-me signal in the phagocytic removal of apoptotic cells in Drosophila and that Draper is a phosphatidylserine-binding receptor for phagocytosis.