Abstract
We have identified and characterized a novel C. elegans gene, ced-12, that functions in the conserved GTPase signaling pathway mediated by CED-2/Crkll, CED-5/DOCK180, and CED-10/Rac to control cell migration and phagocytosis of apoptotic cells. We provide evidence that ced-12 likely acts upstream of ced-10 during cell migration and phagocytosis and that CED-12 physically interacts with CED-5 and forms a ternary complex with CED-2 in vitro. We propose that the formation and localization of a CED-2-CED-5-CED-12 ternary complex to the plasma membrane activates CED-10, leading to the cytoskeletal reorganization that occurs in the polarized extension of cell surfaces in engulfing cells and migrating cells. We suggest that CED-12 counterparts in higher organisms regulate cytoskeleton dynamics, as CED-12 does in C. elegans.
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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Amino Acid Sequence
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Animals
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Animals, Genetically Modified
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Apoptosis / physiology
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Apoptosis Regulatory Proteins
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Caenorhabditis elegans
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Caenorhabditis elegans Proteins*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Movement / physiology*
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Cloning, Molecular
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Conserved Sequence
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Cytoskeletal Proteins*
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Helminth Proteins / metabolism
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Membrane Proteins / metabolism
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Molecular Sequence Data
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Mutation / physiology
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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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rac GTP-Binding Proteins / metabolism*
Substances
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Apoptosis Regulatory Proteins
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CED-10 protein, C elegans
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CED-12 protein, C elegans
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CED-5 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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Helminth Proteins
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Membrane 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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Protein Kinases
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rac GTP-Binding Proteins