CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans.
Engulfment of apoptotic cells in Caenorhabditis elegans is controlled by two partially redundant pathways. Mutations in genes in one of these pathways, defined by the genes ced-2, ced-5 and ced-10, result in defects both in the engulfment of dying cells and in the migrations of the two distal tip cells of the developing gonad. Here we find that ced-2 and ced-10 encode proteins similar to the human adaptor protein CrkII and the human GTPase Rac, respectively. Together with the previous observation that ced-5 encodes a protein similar to human DOCK180, our findings define a signalling pathway that controls phagocytosis and cell migration. We provide evidence that CED-2 and CED-10 function in engulfing rather than dying cells to control the phagocytosis of cell corpses, that CED-2 and CED-5 physically interact, and that ced-10 probably functions downstream of ced-2 and ced-5. We propose that CED-2/CrkII and CED-5/DOCK180 function to activate CED-10/Rac in a GTPase signalling pathway that controls the polarized extension of cell surfaces.
Reddien
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PW
Howard Hughes Medical Institute, Department of Biology, 68-425, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Horvitz
H R
HR
D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000276:immunology; D029742:Caenorhabditis elegans Proteins; D002465:Cell Movement / Q000235:genetics* / Q000276:immunology; D006066:Gonads / Q000166:cytology; D018869:Heat-Shock Response / Q000235:genetics; D015801:Helminth Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010587:Phagocytosis / Q000235:genetics* / Q000276:immunology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
C111579:CED-5 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D011494:Protein Kinases; D020744:rac GTP-Binding Proteins