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Article
Subject Categories: Cell & Tissue Architecture | Development
The EMBO Journal (2007) 26, 5083–5092, doi:10.1038/sj.emboj.7601922
Published online 8 November 2007
RAP-1 and the RAL-1/exocyst pathway coordinate hypodermal cell organization in Caenorhabditis elegans
Ester W Frische1, Wendy Pellis-van Berkel1, Gijs van Haaften2, Edwin Cuppen2, Ronald H A Plasterk2, Marcel Tijsterman2, Johannes L Bos1 and Fried J T Zwartkruis1
1 Department of Physiological Chemistry, Centre for Biomedical Genetics, UMC Utrecht, Utrecht, The Netherlands
2 Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht, The Netherlands

To whom correspondence should be addressed
Fried J T Zwartkruis, Department of Physiological Chemistry, Centre for Biomedical Genetics, UMC Utrecht, Universiteitsweg 100, Utrecht 3584 CG, The Netherlands. Tel.: +31 30 2533992; Fax +31 30 2539035; E-mail: G.J.T.zwartkruis@umcutrecht.nl

Received 27 April 2007; Accepted 19 October 2007; Published online 8 November 2007.
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.
Keywords: adherens junction, embryogenesis, Ral, Rap1, synthetic lethality
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