Arrow, an LDL-receptor related protein, functions as a Wg receptor subunit and interacts with Axin. M. Wehrli 1, N. Erdeniz 2, A. Rives 3, S. DiNardo 3. 1) Cell & Dev Biol/L215, Oregon Health & Science University, Portland, OR; 2) Department of Molecular & Medical Genetics, Oregon Health Sciences University, Portland, OR; 3) Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA, USA, 19104.
The Wnt/Wingless pathway is essential for the patterning many tissues. We showed that Drosophila arrow encodes a novel component in the Wg pathway and that Arrow is a protein homologous to LDL receptor related proteins. Arrow is required in the cell that receives the Wg signal. Based on epistasis mapping and protein localization data, Arrow functions at the plasma membrane. Since Wg-binding proteins of the Frizzled family also localize to the cell membrane, Frizzleds (DFz and DFz2) and Arrow may function as subunits of a Wg receptor. Consistent with this co-receptor model, we showed that over-expression of Arrow, like over-expression of DFz2, potentiates Wg signaling. We tested this model further and provide here in vivo evidence that the intimate association of Arrow and DFz2 is necessary for Wg signaling. This indicates that the Wg receptor consists of the two subunits, Arrow and Frizzleds (DFz, DFz2). In extending our analysis to the intracellular components we found that the receptor subunit Arrow interacts with the downstream scaffold protein Axin. We show that this interaction potentiates Wg signaling by negatively regulating the binding of Axin to Armadillo. This then allows Armadillo to signal by entering the nucleus and activating transcription.