Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Animals, Genetically Modified
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Apoptosis Regulatory Proteins
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Caenorhabditis elegans / cytology
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins*
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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Cell Movement / physiology*
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Cell Surface Extensions / metabolism
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Cytoskeletal Proteins*
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Cytoskeleton / metabolism
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Flow Cytometry
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Genes, Helminth
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Genes, Reporter
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Gonads / growth & development
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Helminth Proteins / genetics
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Helminth Proteins / metabolism*
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Humans
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Male
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Mice
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Microscopy, Fluorescence
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Molecular Sequence Data
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Phagocytosis / physiology*
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Protein Kinases / metabolism
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Proteins / metabolism
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Proto-Oncogene Proteins c-crk
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Proto-Oncogene Proteins*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Sequence Alignment
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Signal Transduction / physiology
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Tissue Distribution
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rac GTP-Binding Proteins / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Apoptosis Regulatory Proteins
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CED-12 protein, C elegans
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Caenorhabditis elegans Proteins
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Carrier Proteins
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Cytoskeletal Proteins
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DOCK1 protein, human
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ELMO2 protein, human
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ELMO3 protein, human
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Elmo2 protein, mouse
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Helminth Proteins
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Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-crk
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Recombinant Fusion Proteins
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Protein Kinases
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rac GTP-Binding Proteins
Associated data
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GENBANK/AF398883
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GENBANK/AF398884
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GENBANK/AF398885
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GENBANK/AF398886