Vascular Morphogenesis is regulated by Wnt signaling via PDZRN3
Role of a novel ubiquitin ligase in Wnt signal transduction during development and in pathology
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This work presents the characterization Of the Ubiquitin Ligase PDZRN3 as a Novel Actor of Wnt Pathways in Vascular Morphogenesis and Integrity. Fzd4 is the only Frizzled receptor that is essential for angiogenesis. By using a yeast two hybrid screening, we have identified the ubiquitin ligase PDZRN3 as a potential partner of the adaptor protein Dvl3 that acts downstream of Fzd4. By using genetic models, we have shown that loss of PDZRN3 leads to early embryo lethality due to vascular defects in the yolk sac when deleted in utero, and is then required during retinal vascularization. PDZRN3 wou...
This work presents the characterization Of the Ubiquitin Ligase PDZRN3 as a Novel Actor of Wnt Pathways in Vascular Morphogenesis and Integrity. Fzd4 is the only Frizzled receptor that is essential for angiogenesis. By using a yeast two hybrid screening, we have identified the ubiquitin ligase PDZRN3 as a potential partner of the adaptor protein Dvl3 that acts downstream of Fzd4. By using genetic models, we have shown that loss of PDZRN3 leads to early embryo lethality due to vascular defects in the yolk sac when deleted in utero, and is then required during retinal vascularization. PDZRN3 would target the Fzd4/ Dvl3 complex to endosome, leading to signal transduction upon binding of Wnt5a to Fzd4. PDZRN3 also regulates integrity of the blood brain barrier by acting on tight junctions stability. Loss of PDZRN3 stabilizes microvessels after cerebral ischemia. PDZRN3 would induce tight junction disruption and blood brain barrier leakage by ubiquitinylating the scaffolding protein MUPP1.
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