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2W Rho1 is involved in multiple morphogenetic processes during Drosophila development. C.R. Magie, S.M. Parkhurst. Division Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109. (206) 667-6489.
Rho GTPases play an important role in diverse biological processes such as actin cytoskeleton organization, gene transcription, cell cycle progression, and adhesion. They are required during early Drosophila development for proper execution of morphogenetic movements of individual cells and groups of cells important for the formation of the embryonic body plan. Embryos homozygous for a Rho1 mutation exhibit a characteristic zygotic phenotype, which includes severe defects in head involution and imperfect dorsal closure. These phenotypes could be due to defective actin cytoskeletal regulation, but may also involve defects in cell adhesion, as we find that cadherin and catenin localization is disrupted in Rho1 mutants. Significantly, we find that Rho1 binds directly to the adherens junction components alpha-catenin and p120ctn in vitro, and these interactions map to distinct surface-exposed regions of the protein not previously assigned functions. In addition, alpha-catenin can be co-immunoprecipitated with Rho1 from embryo lysates. Our observations suggest that alpha-catenin and p120ctn are key players in a mechanism of recruiting Rho1 to its sites of action. Reduction of maternal Rho1 activity results in disrupted actin cytoskeleton during oogenesis and embryos display patterning defects as a result of improper maintenance of segmentation gene expression. This effect of Rho1 on signaling suggests a direct role in the transduction of the signal, but may also be due to aberrant cytoskeletal regulation. Current studies are aimed at distinguishing between these possibilities.
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