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

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 Gα_12, Gα_i1, Gα_oA, Gα_s, or Gα_q. Stimulation with the FZD agonist WNT induced the dissociation of the Gα₁₃ protein from FZD₁₀, and led to global Gα_12/13-dependent cell changes assessed by dynamic mass redistribution measurements. Furthermore, we show that FZD₁₀ mediates Gα_12/13 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.