Membrane-tethered Drosophila Armadillo cannot transduce Wingless signal onits own

Drosophila Armadillo and its vertebrate homolog beta-catenin are key effect ors of Wingless/Wnt signaling. In the current model, Wingless/Wnt signal st abilizes Armadillo/beta-catenin, which then accumulates in nuclei and binds TCF/LEF family proteins, forming bipartite transcription factors which act ivate transcription of Wingless/Wnt responsive genes. This model was recent ly challenged. Overexpression in Xenopus of membrane-tethered beta-catenin or its paralog plakoglobin activates Wnt signaling, suggesting that nuclear localization of Armadillo/beta-catenin is not essential for signaling. Tet hered plakoglobin or beta-catenin might signal on their own or might act in directly by elevating levels of endogenous beta-catenin, We tested these hy potheses in Drosophila by removing endogenous Armadillo. We generated a ser ies of mutant Armadillo proteins with altered intracellular localizations, and expressed these in wild-type and armadillo mutant backgrounds. We found that membrane-tethered Armadillo cannot signal on its own; however it can function in adherens junctions. We also created mutant forms of Armadillo c arrying heterologous nuclear localization or nuclear export signals, Althou gh these signals alter the subcellular localization of Arm when overexpress ed in Xenopus, in Drosophila they have little effect on localization and on ly subtle effects on signaling. This supports a model in which Armadillo's nuclear localization is key for signaling, but in which Armadillo intracell ular localization is controlled by the availability and affinity of its bin ding partners.