Frizzled–PDZ scaffold interactions in the control of Wnt signaling

Wnt signaling pathways are essential for embryonic patterning and are disturbed in a wide spectrum of diseases, including cancer. An unresolved question is how the different Wnt pathways are supported and regulated. Here, we review how the PDZ domain-interacting C-terminal region of the Wnt receptor Frizzled can impact on the outcome of Wnt signaling. PDZ domains are interaction domains often found in multi-domain scaffolding proteins. PDZ scaffolds assemble specific proteins into large molecular complexes at defined locations in the cell but can also regulate the dynamic trafficking of target proteins. The impact of PDZ proteins in Wnt signaling has probably been underinvestigated and further studies might help to understand several unresolved aspects.