Abstract
During apoptosis, dying cells are swiftly removed by phagocytes. It is not fully understood how apoptotic cells are recognized by phagocytes. Here we report the identification and characterization of the Caenorhabditis elegans ttr-52 gene, which encodes a transthyretin-like protein and is required for efficient cell corpse engulfment. The TTR-52 protein is expressed in, and secreted from, C. elegans endoderm and clusters around apoptotic cells. Genetic analysis indicates that TTR-52 acts in the cell corpse engulfment pathway mediated by CED-1, CED-6 and CED-7 and affects clustering of the phagocyte receptor CED-1 around apoptotic cells. TTR-52 recognizes surface-exposed phosphatidylserine (PtdSer) in vivo and binds to both PtdSer and the extracellular domain of CED-1 in vitro. TTR-52 is therefore the first bridging molecule identified in C. elegans that mediates recognition of apoptotic cells by crosslinking the PtdSer 'eat me' signal with the phagocyte receptor CED-1.
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Acknowledgements
We thank J. McGhee for the Pges-1GFP construct and T. Blumenthal for comments and discussion on the manuscript. This work was supported by a Burroughs Wellcome Fund Award (D.X.), NIH R01 grants GM59083 and GM79097 (D.X.), and the National High Technology Project 863 of China (X.C.W).
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X.C.W. and W.D.L. performed most of the genetic and cell biological experiments. D.F.Z. performed both PtdSer binding experiments and in vitro protein interaction assays. Y.S. performed immunoprecipitation experiments in C. elegans. B.L., B.H.C., P.F.G. and X.G. performed some of the genetic and cell biological experiments. H.W.Y. performed the initial in vitro PtdSer binding experiments and E. P. conducted a bioinformatic analysis of TTR family proteins. Z.H.S., E.K.N. and S.M. contributed to the generation of strains. X.C.W. and D.X. designed the experiments and wrote the paper.
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Wang, X., Li, W., Zhao, D. et al. Caenorhabditis elegans transthyretin-like protein TTR-52 mediates recognition of apoptotic cells by the CED-1 phagocyte receptor. Nat Cell Biol 12, 655–664 (2010). https://doi.org/10.1038/ncb2068
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DOI: https://doi.org/10.1038/ncb2068
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