show("a")-catenin and regulates cadherin-based adherens junction components."> Rho1 interacts with p120ctn and -catenin and regulates cadherin-based adherens junction components. S. Parkhurst, C. Magie, A. Rosales-Nieves, J. Johndrow, S. Parks. Div Basic Sci, Fred Hutchinson Cancer Res Ctr, Seattle, WA.

   Rho GTPases play a central role in diverse biological processes such as actin cytoskeleton organization, microtubule dynamics, gene transcription, oncogenic transformation, cadherin-mediated adhesion and epithelial wound repair. We have characterized a loss-of-function mutation in the Drosophila RhoA homologue, Rho1. We find that embryos homozygous for the Rho1 mutation exhibit a characteristic zygotic phenotype that includes severe defects in head involution and imperfect dorsal closure. We are currently investigating the molecular mechanisms associated with specific dRho1 regulatory pathways mediated through its interactions with - and p120- catenin, proteins involved in adherens junction formation, and concertina, a G-like protein. We find that Rho1 interacts genetically and physically with -catenin, p120ctn, and concertina. For the catenin proteins these interactions map to distinct surface-exposed regions of the protein not previously assigned functions. While Rho1 protein is present throughout the cell, it accumulates apically, particularly at sites of cadherin-based adherens junctions. Cadherin and catenin localization is disrupted in Rho1 mutants, implicating Rho1 in their regulation. p120ctn has recently been suggested to inhibit Rho activity through an unknown mechanism. We find that Rho1 accumulates in response to lowered p120ctn activity. Significantly, we find that removal of p120ctn activity chronically (via mutation) compared to catastrophically (via RNAi) leads to different phenotypes and is consistent with a model in which there is a delicate balance in the cell between complexes containing these proteins. These observations suggest that -catenin and p120ctn are key players in a mechanism of recruiting Rho1 to its sites of action.