DIFFERENTIAL RECRUITMENT OF DISHEVELLED PROVIDES SIGNALING SPECIFICITY IN THE PLANAR CELL POLARITY AND WINGLESS SIGNALING PATHWAYS

In Drosophila, planar cell polarity (PCP) signaling is mediated by the receptor Frizzled (Fz) and transduced by Dishevelled (Dsh). Wingless (Wg) signaling also requires Dsh and may utilize DFz2 as a receptor. U sing a heterologous system, we show that Dsh is recruited selectively to the membrane by Fz but not DFz2, and this recruitment depends on th e DEP domain but not the PDZ domain in Dsh. A mutation in the DEP doma in impairs both membrane localization and the function of Dsh in PCP s ignaling, indicating that translocation is important for function. Fur ther genetic and molecular analyses suggest that conserved domains in Dsh function differently during PCP and Wg signaling, and that diverge nt intracellular pathways are activated. We propose that Dsh has disti nct roles in PCP and Wg signaling. The BCP signal may selectively resu lt in focal Fz activation and asymmetric relocalization of Dsh to the membrane, where Dsh effects cytoskeletal reorganization to orient preh air initiation.