title: CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Biology, 68-425, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Reddien
authors.forename: H R
authors.initials: HR
authors.lastname: Horvitz
mesh_terms: 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
chemical_list: 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