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.

Molecular Cellular and Pharmacobiology Section Institute for Pharmaceutical Biology University of Bonn Bonn Germany

Science for Life Laboratory Department of Neuroscience Karolinska Institute SE 171 77 Stockholm Sweden

Science for Life Laboratory KTH Royal Institute of Technology SE 17121 Stockholm Sweden

Section of Receptor Biology and Signaling Dept Physiology and Pharmacology Karolinska Institutet S17177 Stockholm Sweden

Section of Receptor Biology and Signaling Dept Physiology and Pharmacology Karolinska Institutet S17177 Stockholm Sweden; Faculty of Science Institute of Experimental Biology Masaryk University Brno Czech Republic

Section of Receptor Biology and Signaling Dept Physiology and Pharmacology Karolinska Institutet S17177 Stockholm Sweden; Section on Molecular Signal Transduction Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health 35A Convent Drive MSC 3752 Bethesda MD 20892 3752 USA

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