Abstract
The small Ras-like GTPase Rap1 has been identified as a regulator of integrin activation and cadherin-mediated cell-cell contacts. Surprisingly, null mutants of RAP-1 in Caenorhabditis elegans are viable and fertile. In a synthetic lethal RNAi screen with C. elegans rap-1 mutants, the Ras-like GTPase ral-1 emerged as one of seven genes specifically required for viability. Depletion of exoc-8 and sec-5, encoding two putative RAL-1 effectors and members of the exocyst complex, also caused lethality of rap-1 mutants, but did not affect wild-type worms. The RAP-1 and the RAL-1/exocyst pathway appear to coordinate hypodermal cell movement and elongation during embryonic development. They mediate their effect in part through targeting the alpha-catenin homologue HMP-1 to the lateral membrane. Genetic interactions show that the RAP-1 and RAL-1/exocyst pathway also act in parallel during larval stages. Together these data provide in vivo evidence for the exocyst complex as a downstream RAL-1 effector in cell migration.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Genetically Modified
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Caenorhabditis elegans / cytology
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Caenorhabditis elegans / embryology*
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Cell Movement / physiology*
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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Embryo, Nonmammalian / anatomy & histology
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Embryo, Nonmammalian / physiology
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Mutation
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Phenotype
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RNA Interference
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Subcutaneous Tissue*
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Vesicular Transport Proteins / genetics
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Vesicular Transport Proteins / metabolism*
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ral GTP-Binding Proteins / genetics
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ral GTP-Binding Proteins / metabolism*
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rap1 GTP-Binding Proteins / genetics
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rap1 GTP-Binding Proteins / metabolism*
Substances
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Caenorhabditis elegans Proteins
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Cytoskeletal Proteins
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Exoc-8 protein, C elegans
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Recombinant Fusion Proteins
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Vesicular Transport Proteins
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RAL-1 protein, C elegans
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ral GTP-Binding Proteins
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rap1 GTP-Binding Proteins