title: Regulation of vascular endothelial barrier function by Epac, a cAMP-activated exchange factor for Rap GTPase.
abstract: Endothelial cell-cell junctional proteins and cortical actin are of central importance for regulating vascular permeability. Rap1, a member of the Ras family of GTPases, is enriched at endothelial cell-cell contacts and activated by cyclic AMP (cAMP) through a PKA-independent pathway. Activation of a cAMP-inducible guanine-exchange factor for Rap, Epac, results in markedly enhanced basal endothelial barrier function by increasing cortical actin and subsequent redistribution of adherens and tight junctional molecules to cell-cell contacts. Activation of Epac also counteracts thrombin-induced hyperpermeability through down-regulation of Rho GTPase activation, suggesting cross-talk between Rap and Rho GT-Pases. Thus, Epac/Rap activation represents a new pathway for regulating endothelial cell barrier function.
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Xavier
authors.initials: X
authors.lastname: Cullere
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Shaw
authors.forename: Lorna
authors.initials: L
authors.lastname: Andersson
authors.forename: Junichi
authors.initials: J
authors.lastname: Hirahashi
authors.forename: Francis W
authors.initials: FW
authors.lastname: Luscinskas
authors.forename: Tanya N
authors.initials: TN
authors.lastname: Mayadas
mesh_terms: D001011:Aorta / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D008954:Models, Biological; D013917:Thrombin / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C116122:RAPGEF3 protein, human; D013917:Thrombin; D020827:rap1 GTP-Binding Proteins