CED-2/CrkII and CED-10/Rac Control Phagocytosis and Cell Migration in Caenorhabditis Elegans

Nat Cell Biol. 2000 Mar;2(3):131-6. doi: 10.1038/35004000.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / immunology
  • Caenorhabditis elegans Proteins*
  • Cell Movement / genetics*
  • Cell Movement / immunology
  • Gonads / cytology
  • Heat-Shock Response / genetics
  • Helminth Proteins / genetics
  • Helminth Proteins / immunology
  • Helminth Proteins / metabolism
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phagocytosis / genetics*
  • Phagocytosis / immunology
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-crk
  • Proto-Oncogene Proteins*
  • Sequence Homology, Amino Acid
  • Signal Transduction / genetics
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism

Substances

  • CED-5 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-crk
  • Protein Kinases
  • rac GTP-Binding Proteins

Associated data

  • GENBANK/AF226866
  • GENBANK/AF226867