FZD(10)-G alpha(13) signalling axis points to a role of FZD(10) in CNS angiogenesis
| Authors | |
|---|---|
| Year of publication | 2017 |
| Type | Article in Periodical |
| Magazine / Source | Cellular Signalling |
| MU Faculty or unit | |
| Citation | |
| Doi | http://dx.doi.org/10.1016/j.cellsig.2017.01.023 |
| Keywords | WNT; FZD; GPCR; Endothelial cell; Angiogenesis; GNA13; YAP/PAZ |
| Description | Among the 10 Frizzled (FZD) isoforms belonging to the Class F of G protein-coupled receptors (GPCRs), FZD(10) remains the most enigmatic. FZD10 shows homology to FZD(4) and FZD(9) and was previously implicated in both beta-catenin-dependent and-independent signalling. In normal tissue, FZD(10) levels are generally very low; however, its upregulation in synovial carcinoma has attracted some attention for therapy. Our findings identify FZD(10), as a receptor interacting with and signalling through the heterotrimeric G protein G alpha(13) but not G alpha(12), G alpha(i1,) G alpha(oA), G alpha(s), or G alpha(q). Stimulation with the FZD agonist WNT induced the dissociation of the G alpha(13) protein from FZD(10), and led to global G alpha(12/13)-dependent cell changes assessed by dynamic mass redistribution measurements. Furthermore, we show that FZD(10) mediates G alpha(12/13) activation-dependent induction of YAP/TAZ transcriptional activity. In addition, we show a distinct expression of FZD(10) in embryonic CNS endothelial cells at E11.5-E14.5. Given the well-known importance of G alpha(13) signalling for the development of the vascular system, the selective expression of FZD(10) in brain vascular endothelial cells points at a potential role of FZD(10)-G alpha(13) signalling in CNS angiogenesis. (C) 2017 Elsevier Inc. All rights reserved. |
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