Abstract
During programmed cell death, cell corpses are rapidly engulfed1. This engulfment process involves the recognition and subsequent phagocytosis of cell corpses by engulfing cells1,2,3,4. How cell corpses are engulfed is largely unknown. Here we report that ced-5, a gene that is required for cell-corpse engulfment in the nematode Caenorhabditis elegans5, encodes a protein that is similar to the human protein DOCK180 and the Drosophila melanogaster protein Myoblast City (MBC), both of which have been implicated in the extension of cell surfaces6. ced-5 mutants are defective not only in the engulfment of cell corpses but also in the migrations of two specific gonadal cells, the distal tip cells. The expression of human DOCK180 in C. elegans rescued the cell-migration defect of a ced-5 mutant. We present evidence that ced-5 functions in engulfing cells during the engulfment of cell corpses. We suggest that ced-5 acts in the extension of the surface of an engulfing cell around a dying cell during programmed cell death. We name this new family of proteins that function in the extension of cell surfaces the CDM (for CED-5, DOCK180 and MBC) family.
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Acknowledgements
We thank members of H.R.H.'s laboratory and C.-L. Wei for their comments, D. Hall and E. Hedgecock for sharing unpublished results regarding DTC migration, R. Barstead and P. Okkema for cDNA libraries, A Coulson for cosmids, H. Hasegawa and M. Matsuda for the DOCK180 cDNA clone, E. James for determining DNA sequences of the RACE product, S. Glass for the ced-5 alleles n2098 and n2099 and J. Harris and C. Kenyon for mu57. H.R.H. is an Investigator of the Howard Hughes Medical Institute. The accession number for the ced-5 sequence is AF038576.
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Wu, YC., Horvitz, H. C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180. Nature 392, 501–504 (1998). https://doi.org/10.1038/33163
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DOI: https://doi.org/10.1038/33163
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