Pathway specificity by the bifunctional receptor frizzled is determined byaffinity for wingless

The Frizzled (Fz) protein in Drosophila is a bifunctional receptor that act s through a GTPase pathway in planar polarity signaling and as a receptor f or Wingless (Wg) using the canonical Wnt pathway. We found that the ligand- binding domain (CRD) of Fz has an approximately 10-fold lower affinity for Wg than the CRD of DFz2, a Wg receptor without polarity activity. When the Fz CRD is replaced by the high-affinity CRD of DFz2, the resulting chimeric protein gains Wg signaling activity, yet also retains polarity signaling a ctivity. In contrast, the reciprocal exchange of the Fz CRD onto DFz2 is no t sufficient to confer polarity activity to DFz2. This suggests that Fz has an intrinsic capacity for polarity signaling and that high-affinity intera ction with Wg couples it to the Wnt pathway.