title: Sphingosine 1-phosphate receptor regulation of N-cadherin mediates vascular stabilization.
abstract: 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.
authors.affiliation: Center for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut 06030-3501, USA.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Paik
authors.forename: Athanasia
authors.initials: A
authors.lastname: Skoura
authors.forename: Sung-Suk
authors.initials: SS
authors.lastname: Chae
authors.forename: Ann E
authors.initials: AE
authors.lastname: Cowan
authors.forename: David K
authors.initials: DK
authors.lastname: Han
authors.forename: Richard L
authors.initials: RL
authors.lastname: Proia
authors.forename: Timothy
authors.initials: T
authors.lastname: Hla
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000502:physiology*; D015820:Cadherins / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D049312:Receptors, Lysophospholipid; D015398:Signal Transduction
chemical_list: D015820:Cadherins; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid