FZD10-Gα13 signalling axis points to a role of FZD10 in CNS angiogenesis

• Published in: Cellular signalling 2017-04, Vol.32, p.93-103
• 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: Angiogenesis; Endothelial cell; FZD; GNA13; GPCR; WNT; YAP/TAZ
• ISSN: 0898-6568; 1873-3913; 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), FZD10 remains the most enigmatic. FZD10 shows homology to FZD4 and FZD9 and was previously implicated in both β-catenin-dependent and –independent signalling. In normal tissue, FZD10 levels are generally very low; however, its upregulation in synovial carcinoma has attracted some attention for therapy. Our findings identify FZD10 as a receptor interacting with and signalling through the heterotrimeric G protein Gα13 but not Gα12, Gαi1, GαoA, Gαs, or Gαq. Stimulation with the FZD agonist WNT induced the dissociation of the Gα13 protein from FZD10, and led to global Gα12/13–dependent cell changes assessed by dynamic mass redistribution measurements. Furthermore, we show that FZD10 mediates Gα12/13 activation-dependent induction of YAP/TAZ transcriptional activity. In addition, we show a distinct expression of FZD10 in embryonic CNS endothelial cells at E11.5–E14.5. Given the well-known importance of Gα13 signalling for the development of the vascular system, the selective expression of FZD10 in brain vascular endothelial cells points at a potential role of FZD10-Gα13 signalling in CNS angiogenesis. [Display omitted] •FZD10 interacts selectively with Gα13 to mediate WNT-induced signalling.•Gα13 mediates FZD10 signalling to the YAP/TAZ pathway.•FZD10 is expressed in CNS endothelial cells during mouse development.•FZD10-Gα13 signalling might play a crucial role in CNS angiogenesis.