Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways

TLDR

In Drosophila, Dishevelled mediates both planar cell polarity and Wingless signaling, with Frizzled and DFz2 acting as receptors, respectively. The study aims to determine whether Dishevelled performs distinct roles in PCP versus Wg signaling. Dishevelled is recruited to the membrane by Frizzled through its DEP domain, leading to cytoskeletal reorganization that orients prehair initiation, whereas DFz2 fails to recruit it. A DEP‑domain mutation abolishes membrane localization and PCP function, and domain‑specific analyses reveal that Dishevelled activates divergent intracellular pathways in PCP and Wg signaling.

Abstract

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. Using a heterologous system, we show that Dsh is recruited selectively to the membrane by Fz but not DFz2, and this recruitment depends on the DEP domain but not the PDZ domain in Dsh. A mutation in the DEP domain impairs both membrane localization and the function of Dsh in PCP signaling, indicating that translocation is important for function. Further genetic and molecular analyses suggest that conserved domains in Dsh function differently during PCP and Wg signaling, and that divergent intracellular pathways are activated. We propose that Dsh has distinct roles in PCP and Wg signaling. The PCP signal may selectively result in focal Fz activation and asymmetric relocalization of Dsh to the membrane, where Dsh effects cytoskeletal reorganization to orient prehair initiation.