Eater, a Transmembrane Protein Mediating Phagocytosis of Bacterial Pathogens in Drosophila

Cell, 123: 335-346 (2005)

Speaker: 陳銘祥                       Time: Feb 22 15:10 -16:00

Commentator:  謝奇璋 老師            Place: 601

Phagocytosis is an evolutionally complex process at the first line to avoid the establishment of infection by pathogens. In Drosophia, a group of cells called plasmatocyte/macrophage constitutes the innate immunity similar to the phagocytes in mammals. To find out the new receptors for recognition of microbes in macrophage-likeDrosophila cell line, S2 cells, the authors conducted an expression profile by DNA microarray analysis. They identified 46 downregulated genes following RNAi targeting of Serpent, a transcription factor required for phagocytosis¹. By knocking down these genes individually, they discovered a gene, eater, that encoded a predicted transmembrane protein involved in phagocytosis in Drosophila. In the absence of eater expression in S2 cells, the binding and internalization of bacteria were decreased. Further, based on the features of the amino acid sequence of the Eater protein, the N-terminal part might be functionally important for ligand binding. Indeed, the purified N-terminal 199 amino acids of the Eater protein directly recognized the bacteria in vitro. The Northern blot and in situ hybridization experiments revealed that eater was expressed specially in plasmatocyte lineage throughout the larval hemocyte development. They then generated the eater null flies to determine the role of the Eater protein in vivo. They observed that the eater null macrophages in late wandering third instar larvae and adult flies were significantly impaired in phagocytosis for bacterial clearance. However, these mutant macrophages were not defective in spreading, adherence or phagocytosis of India ink particles. In addition, in a natural oral infection model, the eater null flies were more sensitive to Serratia marcescens than normal adult flies. In summary, the Eater protein was shown to be a new receptor for microbes and play an important role in phagocytosis of bacterial pathogens in Drosophila.  

References
1. Rämet, M., Manfruelli, P., Pearson, A. et al. (2002). Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli. Nature 416, 644–648.

2. Kocks C., Rämet, M., Ju Hyun Cho et al. (2005). Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila. Cell 123, 335-346.