title: FZD10-Gα13signalling axis points to a role of FZD10in CNS angiogenesis.
abstract: Among the 10 Frizzled (FZD) isoforms belonging to the Class F of G protein-coupled receptors (GPCRs), FZD10remains the most enigmatic. FZD10shows homology to FZD4and FZD9and was previously implicated in both β-catenin-dependent and -independent signalling. In normal tissue, FZD10levels are generally very low; however, its upregulation in synovial carcinoma has attracted some attention for therapy. Our findings identify FZD10as a receptor interacting with and signalling through the heterotrimeric G protein Gα13but not Gα12,Gαi1,GαoA,Gαs, or Gαq. Stimulation with the FZD agonist WNT induced the dissociation of the Gα13protein from FZD10, and led to global Gα12/13-dependent cell changes assessed by dynamic mass redistribution measurements. Furthermore, we show that FZD10mediates Gα12/13activation-dependent induction of YAP/TAZ transcriptional activity. In addition, we show a distinct expression of FZD10in embryonic CNS endothelial cells at E11.5-E14.5. Given the well-known importance of Gα13signalling for the development of the vascular system, the selective expression of FZD10in brain vascular endothelial cells points at a potential role of FZD10-Gα13signalling in CNS angiogenesis.
authors.affiliation: Section of Receptor Biology & Signaling, Dept. Physiology & Pharmacology, Karolinska Institutet, S17177 Stockholm, Sweden.
authors.forename: Belma
authors.initials: B
authors.lastname: Hot
authors.affiliation: Section of Receptor Biology & Signaling, Dept. Physiology & Pharmacology, Karolinska Institutet, S17177 Stockholm, Sweden.
authors.forename: Jana
authors.initials: J
authors.lastname: Valnohova
authors.affiliation: Section of Receptor Biology & Signaling, Dept. Physiology & 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.
authors.forename: Elisa
authors.initials: E
authors.lastname: Arthofer
authors.affiliation: Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Simon
authors.affiliation: Science for Life Laboratory, Department of Neuroscience, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Jaekyung
authors.initials: J
authors.lastname: Shin
authors.affiliation: Science for Life Laboratory, KTH-Royal Institute of Technology, SE-17121 Stockholm, Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.affiliation: Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany.
authors.forename: Evi
authors.initials: E
authors.lastname: Kostenis
authors.affiliation: Science for Life Laboratory, Department of Neuroscience, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Mulder
authors.affiliation: Section of Receptor Biology & Signaling, Dept. Physiology & Pharmacology, Karolinska Institutet, S17177 Stockholm, Sweden; Faculty of Science, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic. Electronic address: gunnar.schulte@ki.se.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Schulte
mesh_terms: D000818:Animals; D002460:Cell Line; D002490:Central Nervous System / Q000098:blood supply*; D000072261:Dishevelled Proteins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D051157:Frizzled Receptors / Q000378:metabolism*; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism*; D006801:Humans; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction; D051153:Wnt Proteins / Q000494:pharmacology
chemical_list: D000072261:Dishevelled Proteins; C121168:FZD10 protein, human; D051157:Frizzled Receptors; C492388:Fzd10 protein, mouse; D051153:Wnt Proteins; D044365:GTP-Binding Protein alpha Subunits, G12-G13
keywords: Angiogenesis; Endothelial cell; FZD; GNA13; GPCR; WNT; YAP/TAZ