CDP-diacylglycerol synthetase-controlled phosphoinositide availability limits VEGFA signaling and vascular morphogenesis
作者： Weijun Pan , Van N. Pham , Amber N. Stratman , Daniel Castranova , Makoto Kamei
DOI: 10.1182/BLOOD-2012-02-408328
关键词: Cell biology 、 Angiogenesis 、 Morphogenesis 、 Phospholipase 、 Biochemistry 、 In vivo 、 Zebrafish 、 Neovascularization 、 Signal transduction 、 Biology 、 Vascular endothelial growth factor A
摘要: Understanding the mechanisms that regulate angiogenesis and translating these into effective therapies are of enormous scientific clinical interests. In this report, we demonstrate central role CDP-diacylglycerol synthetase (CDS) in regulation VEGFA signaling angiogenesis. CDS activity maintains phosphoinositide 4,5 bisphosphate (PIP2) availability through resynthesis phosphoinositides, whereas VEGFA, mainly phospholipase Cγ1, consumes PIP2 for signal transduction. Loss CDS2, 1 2 vertebrate enzymes, results vascular-specific defects zebrafish vivo failure VEGFA-induced endothelial cells vitro. Absence CDS2 also reduced arterial differentiation angiogenic signaling. deficit-caused phenotypes can be successfully rescued by artificial elevation levels, excess or increased promote These suggest CDS-controlled phosphoinositides is essential
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