| First Author | Paik JH | Year | 2004 |
| Journal | Genes Dev | Volume | 18 |
| Issue | 19 | Pages | 2392-403 |
| PubMed ID | 15371328 | Mgi Jnum | J:93030 |
| Mgi Id | MGI:3055628 | Doi | 10.1101/gad.1227804 |
| Citation | Paik JH, et al. (2004) Sphingosine 1-phosphate receptor regulation of N-cadherin mediates vascular stabilization. Genes Dev 18(19):2392-403 |
| abstractText | Vascular stabilization, a process by which nascent vessels are invested with mural cells, is important in angiogenesis. Here we describe the molecular basis of vascular stabilization regulated by sphingosine 1-phosphate (S1P), a platelet-derived lipid mediator. S1P1 receptor-dependent cell-surface trafficking and activation of the cell-cell adhesion molecule N-cadherin is essential for interactions between endothelial and mural cells. Endothelial cell S1P1/Gi/Rac pathway induces microtubule polymerization, resulting in trafficking of N-cadherin to polarized plasma membrane domains. S1P treatment modulated the phosphorylation of N-cadherin as well as p120-catenin and induced the formation of cadherin/catenin/actin complexes containing novel regulatory and trafficking factors. The net result of endothelial cell S1P1 receptor activation is the proper trafficking and strengthening of N-cadherin-dependent cell-cell adhesion with mural cells. Perturbation of N-cadherin expression with small interfering RNA profoundly attenuated vascular stabilization in vitro and in vivo. S1P-induced trafficking and activation of N-cadherin provides a novel mechanism for the stabilization of nascent blood vessels by mural cells and may be exploited to control angiogenesis and vascular diseases. |
