The removal of apoptotic cells by phagocytic neighbors is essential for metazoan development but remains poorly characterized. Here we report the discovery of a Drosophila phagocytosis receptor, Six-microns-under (SIMU), which is expressed in highly phagocytic cell types during development and required for efficient apoptotic cell clearance by glia in the nervous system and by macrophages elsewhere. SIMU is part of a conserved family of proteins that includes CED-1 and Draper (DRPR). Phenotypic analysis reveals that simu acts upstream of drpr in the same pathway and affects the recognition and engulfment of apoptotic cells, while drpr affects their subsequent degradation. SIMU strongly binds to apoptotic cells, presumably through its EMILIN-like domain, but requires no membrane anchoring, suggesting that it can function as a bridging molecule. Our study introduces an important factor in tissue-resident apoptotic clearance and underscores the prominent role of glia as "semiprofessional" phagocytes in the nervous system.
Bibliographical noteFunding Information:
We would like to thank V. Auld, M. Freeman, L. Luo, P. Martin, Y. Nakanishi, H. Steller, K. White, the Bloomington Stock Center, the Drosophila Genomics Resource Center, and the Developmental Studies Hybridoma Bank for fly strains, cDNAs, and antibodies. We also thank A. North and her staff at the Rockefeller Bioimaging Facility for superb technical support; E. Arama and H. Steller for sharing their insights on apoptosis; and M. Boutros, M. Raff, and H. Steller for comments on the manuscript. We are very much indebted to all members of the Gaul lab for their continuing support and constructive criticism throughout the project, in particular T. Das for advice on the design of the simu knockout, J. Fak for northern analysis and transgene injections, M. Schroeder for assistance with sequence analysis and alignments, and U. Unnerstall for his help with image analysis and figure design. We gratefully acknowledge financial support by a Rockefeller University Women & Science Fellowship (E. K.) and from the NIH (U.G., grant no. EY011560).
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)