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Cell Signal. 2017 Apr;32:93-103. doi: 10.1016/j.cellsig.2017.01.023. Epub 2017 Jan 24.

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

Author information

1
Section of Receptor Biology & Signaling, Dept. Physiology & Pharmacology, Karolinska Institutet, S17177 Stockholm, Sweden.
2
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.
3
Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany.
4
Science for Life Laboratory, Department of Neuroscience, Karolinska Institute, SE-171 77 Stockholm, Sweden.
5
Science for Life Laboratory, KTH-Royal Institute of Technology, SE-17121 Stockholm, Sweden.
6
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.

Abstract

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,i1,oA,s, 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.

KEYWORDS:

Angiogenesis; Endothelial cell; FZD; GNA13; GPCR; WNT; YAP/TAZ

PMID:
28126591
DOI:
10.1016/j.cellsig.2017.01.023
[Indexed for MEDLINE]

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