Gαs Relays Sphingosine-l-Phosphate Receptor 1 Signaling to Stabilize Vascular Endothelial-Cadherin at Endothelial Junctions to Control Mouse Embryonic Vascular Integrity

• Published in: 遗传学报：英文版 no. 11; pp. 613 - 624
• Main Author: Ximing Shao Ke Liu Yi Fan Zhihao Ding Min Chen Minyan Zhu Lee S. Weinstein Hongchang Li Huashun Li
• Format: Journal Article
• Language: English
• Published: 2015
• Subjects: 1-磷酸鞘氨醇; G蛋白偶联受体; 内皮细胞; 小鼠胚胎; 稳定性; 继电器; 血管内皮生长因子受体; 连接控制
• ISSN: 1673-8527

Sphingosine-1-phosphate receptor 1 （S1PR1）, a G protein-coupled recep （GPCR）. controls vasct stability by stabilizing vascular endothelial （VE）-cadherin junctional localization and inhibiting vascular endothelial growth factor receptor 2（VEGFR2） signaling. However, the molecular mechanisms that link S1PR1 signaling to intracellular effectors remain unknown.In this study,we demonstrate that the heterotrimeric G protein subfamily member Gαs, encoded by GNAS,acts as a relay mediator of S1PR1 signaling to control vascular integrity by stabilizing VE-cadherin at endothelial junctions. The endothelial cell -spectific deletion of Gαs in mice causes early embryonic lethality with massive hemorrhage and a disorganized Vaseuiature.The immunostaining results revealed that Gαs deletion remarkably reduces the junctional localization of VE-cadherin, whereas the mull cell coverage of the vessels is not impaired.In addition, we found-that Gαs depletion blocks the S1PR1-activation induced VE-cadherin stabilization at junctons,supporting that Gαs acts downstream of S1PR1 signaling ThuS, our results demonstrate that Gαs is an essential mediator to relay S1PR1 signaling and maintain vascular integrity.