Role of drosophila kinesin II in wingless signaling

Abstract

Wingless (Wg)/Wnt signaling is fundamental in metazoan development. Armadillo (Arm)/ $\beta$ -catenin and Dishevelled (Dsh) are key components of Wnt signal transduction. Recent studies suggest that intracellular trafficking of Wnt signaling components is important, but underlying mechanisms are not well known. Here we show that Klp64D, the Drosophila homolog of Kif3A kinesin II subunit, is required for Wg signaling by regulating Arm during wing development. Mutations in klp64D or RNAi cause wing notching and loss of Wg target gene expression. The wing notching phenotype by Klp64D knockdown is suppressed by activated Arm but not by Dsh, suggesting that Klp64D is required for Arm function. Further, klp64D and arm mutants show synergistic genetic interaction. Consistent with the genetic interaction, Klp64D directly binds to the Arm repeat domain of Arm and can recruit Dsh in the presence of Arm. Overexpression of Klp64D proteins mutated in the motor domain causes dominant wing notching, indicating the importance of the motor activity. Klp64D shows overlapping subcellular localization with Arm and Dsh to intracellular vesicles. In klp64D mutant, Arm is abnormally accumulated in vesicular structures including Golgi, suggesting that intracellular trafficking of Arm is affected. Taken together, it is proposed that Klp64D is essential for Wg signaling by trafficking of Arm via the formation of a conserved complex with Arm.