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Wnts are secreted proteins that are essential for a wide array of developmental and physiological processes. They signal across the plasma membrane by interacting with serpentine receptors of the Frizzled (Fz) family and members of the low-density-lipoprotein-related protein (LRP) family. Activation of Fz-LRP promotes the stability and nuclear localization of β-catenin by compromising the ability of a multiprotein complex containing axin, adenomatosis polyposis coli (APC) and glycogen synthase kinase 3 (GSK3) to target it for degradation and block its nuclear import. The Fz-LRP receptor complex probably accomplishes this by generating multiple signals in the cytoplasm. These involve activation of Dishevelled (Dsh), possibly through trimeric G proteins and LRP-mediated axin binding and/or degradation. However, individual Wnts and Fzs can activate both β-catenin-dependent and -independent pathways, and Fz co-receptors such as LRP probably provide some of this specificity. Additional, conflicting data concern the role of the atypical receptor tyrosine kinase Ryk, which might mediate Wnt signaling independently of Fz and/or function as a Fz co-receptor in some cells.

In Drosophila wing imaginal discs, the Wingless (Wg) protein acts as a morphogen, emanating from the dorsal/ventral (D/V) boundary of the disc to directly define cell identities along the D/V axis at short and long range. Here, we show that high levels of a Wg receptor, Drosophila frizzled 2 (Dfz2), stabilize Wg, allowing it to reach cells far from its site of synthesis. Wg signaling represses Dfz2 expression, creating a gradient of decreasing Wg stability moving toward the D/V boundary. This repression of Dfz2 is crucial for the normal shape of Wg morphogen gradient as well as the response of cells to the Wg signal. In contrast to other ligand-receptor relationships where the receptor limits diffusion of the ligand, Dfz2 broadens the range of Wg action by protecting it from degradation.