CED-12/ELMO, a Novel Member of the CrkII/Dock180/Rac Pathway, Is Required for Phagocytosis and Cell Migration
Copyright policy )CED-12/ELMO, a Novel Member of the CrkII/Dock180/Rac Pathway, Is Required for Phagocytosis and Cell Migration
The C. elegans genes ced-2, ced-5, and ced-10, and their mammalian homologs crkII, dock180, and rac1, mediate cytoskeletal rearrangements during phagocytosis of apoptotic cells and cell motility. Here, we describe an additional member of this signaling pathway, ced-12, and its mammalian homologs, elmo1 and elmo2. In C. elegans, CED-12 is required for engulfment of dying cells and for cell migrations. In mammalian cells, ELMO1 functionally cooperates with CrkII and Dock180 to promote phagocytosis and cell shape changes. CED-12/ELMO-1 binds directly to CED-5/Dock180; this evolutionarily conserved complex stimulates a Rac-GEF, leading to Rac1 activation and cytoskeletal rearrangements. These studies identify CED-12/ELMO as an upstream regulator of Rac1 that affects engulfment and cell migration from C. elegans to mammals.
- University of Virginia United States
- Washington University in St. Louis United States
- United States University United States
- University of Zurich Switzerland
- Stony Brook University United States
Male, Cell Line, Animals, Genetically Modified, Rho, 1300 General Biochemistry, Genetics and Molecular Biology, Cell Movement, Genes, Reporter, C elegans, Animals, Humans, Amino Acid Sequence, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Gonads, GTPase, Cytoskeleton, Genes, Helminth, Adaptor Proteins, Signal Transducing, Biochemistry, Genetics and Molecular Biology(all), G protein, Helminth Proteins, Flow Cytometry, 10124 Institute of Molecular Life Sciences, Rac, protein types, Cytoskeletal Proteins, 570 Life sciences; biology, Cell Surface Extensions, Apoptosis Regulatory Proteins, Carrier Proteins
Male, Cell Line, Animals, Genetically Modified, Rho, 1300 General Biochemistry, Genetics and Molecular Biology, Cell Movement, Genes, Reporter, C elegans, Animals, Humans, Amino Acid Sequence, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Gonads, GTPase, Cytoskeleton, Genes, Helminth, Adaptor Proteins, Signal Transducing, Biochemistry, Genetics and Molecular Biology(all), G protein, Helminth Proteins, Flow Cytometry, 10124 Institute of Molecular Life Sciences, Rac, protein types, Cytoskeletal Proteins, 570 Life sciences; biology, Cell Surface Extensions, Apoptosis Regulatory Proteins, Carrier Proteins
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