C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180.
During programmed cell death, cell corpses are rapidly engulfed. This engulfment process involves the recognition and subsequent phagocytosis of cell corpses by engulfing cells. 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 elegans, 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 surfaces. 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.
Wu
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Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Horvitz
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D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D002465:Cell Movement; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D017238:Genes, Helminth; D005854:Germ Cells / Q000166:cytology; D018869:Heat-Shock Response; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019476:Insect Proteins / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D010587:Phagocytosis / Q000502:physiology*; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D020744:rac GTP-Binding Proteins
C111579:CED-5 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; C099818:DOCK1 protein, human; D029721:Drosophila Proteins; D015801:Helminth Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D011506:Proteins; C107441:mbc protein, Drosophila; D020744:rac GTP-Binding Proteins