FZD 10 -Gα 13 signalling axis points to a role of FZD 10 in CNS angiogenesis

• Published in: Cellular signalling 2017-04, Vol.32, p.93
• Main Authors: Hot, Belma, Valnohova, Jana, Arthofer, Elisa, Simon, Katharina, Shin, Jaekyung, Uhlén, Mathias, Kostenis, Evi, Mulder, Jan, Schulte, Gunnar
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Central Nervous System - blood supply; Dishevelled Proteins - metabolism; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Female; Frizzled Receptors - metabolism; GTP-Binding Protein alpha Subunits, G12-G13 - metabolism; Humans; Mice, Inbred C57BL; Neovascularization, Physiologic; Protein Binding - drug effects; Signal Transduction; Wnt Proteins - pharmacology
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2017.01.023

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.