title: RAP-1 and the RAL-1/exocyst pathway coordinate hypodermal cell organization in Caenorhabditis elegans.
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.
authors.affiliation: Department of Physiological Chemistry, Centre for Biomedical Genetics, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Ester W
authors.initials: EW
authors.lastname: Frische
authors.forename: Wendy
authors.initials: W
authors.lastname: Pellis-van Berkel
authors.forename: Gijs
authors.initials: G
authors.lastname: van Haaften
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.forename: Ronald H A
authors.initials: RH
authors.lastname: Plasterk
authors.forename: Marcel
authors.initials: M
authors.lastname: Tijsterman
authors.forename: Johannes L
authors.initials: JL
authors.lastname: Bos
authors.forename: Fried J T
authors.initials: FJ
authors.lastname: Zwartkruis
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology; D009154:Mutation; D010641:Phenotype; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D040521:Subcutaneous Tissue; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020725:ral GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020827:rap1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; C527106:Exoc-8 protein, C elegans; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins; C000604581:RAL-1 protein, C elegans; D020725:ral GTP-Binding Proteins; D020827:rap1 GTP-Binding Proteins