| First Author | Shao X | Year | 2015 |
| Journal | J Genet Genomics | Volume | 42 |
| Issue | 11 | Pages | 613-624 |
| PubMed ID | 26674379 | Mgi Jnum | J:314577 |
| Mgi Id | MGI:6822815 | Doi | 10.1016/j.jgg.2015.08.006 |
| Citation | Shao X, et al. (2015) Galphas Relays Sphingosine-1-Phosphate Receptor 1 Signaling to Stabilize Vascular Endothelial-Cadherin at Endothelial Junctions to Control Mouse Embryonic Vascular Integrity. J Genet Genomics 42(11):613-624 |
| abstractText | Sphingosine-1-phosphate receptor 1 (S1PR1), a G protein-coupled receptor (GPCR), controls vascular 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 Galphas, 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-specific deletion of Galphas in mice causes early embryonic lethality with massive hemorrhage and a disorganized vasculature. The immunostaining results revealed that Galphas deletion remarkably reduces the junctional localization of VE-cadherin, whereas the mural cell coverage of the vessels is not impaired. In addition, we found that Galphas depletion blocks the S1PR1-activation induced VE-cadherin stabilization at junctions, supporting that Galphas acts downstream of S1PR1 signaling. Thus, our results demonstrate that Galphas is an essential mediator to relay S1PR1 signaling and maintain vascular integrity. |
