FZD-Gα signalling axis points to a role of FZD in CNS angiogenesis.

Among the 10 Frizzled (FZD) isoforms belonging to the Class F of G protein-coupled receptors (GPCRs), FZD remains the most enigmatic. FZD shows homology to FZD and FZD and was previously implicated in both β-catenin-dependent and -independent signalling. In normal tissue, FZD levels are generally very low; however, its upregulation in synovial carcinoma has attracted some attention for therapy. Our findings identify FZD as a receptor interacting with and signalling through the heterotrimeric G protein Gα but not Gα Gα Gα Gα, or Gα. Stimulation with the FZD agonist WNT induced the dissociation of the Gα protein from FZD, and led to global Gα-dependent cell changes assessed by dynamic mass redistribution measurements. Furthermore, we show that FZD mediates Gα activation-dependent induction of YAP/TAZ transcriptional activity. In addition, we show a distinct expression of FZD in embryonic CNS endothelial cells at E11.5-E14.5. Given the well-known importance of Gα signalling for the development of the vascular system, the selective expression of FZD in brain vascular endothelial cells points at a potential role of FZD-Gα signalling in CNS angiogenesis.