FIGURE 7:

Fuzzy delivers Dvl to the cilium via Rab8(+) vesicular traffic and arbitrates relative activity of canonical and noncanonical (PCP) Wnt pathways. In ciliated cells, Fuzzy is required to recruit Rab8 and Dvl2 to the polarized trafficking route, which brings both molecules to the primary cilium. Sequestration of Dvl2 into vesicles depletes intracellular Dvl2 available for canonical Wnt signaling. At the cilium of wild-type cells, Dvl2 coordinates basal body polarization and facilitates PCP signaling. In the absence of Fuzzy, the Rab8-trafficking route is disrupted, ciliogenesis is compromised, and Dvl2 recruitment to the basal bodies is disturbed. Although noncanonical Wnt signaling is defective, the canonical Wnt/β-catenin signaling is hyperactive due to the greater availability of intracellular Dvl2.