Epac1 and PDZ-GEF cooperate in Rap1 mediated endothelial junction control

► Rap1 activity is regulated by both PDZ-GEF and Epac1 to control endothelial barrier. ► Epac1 and Rap1 enhance barrier function by inducing junctional actin. ► PDZ-GEF and Rap1 are required for basal endothelial barrier function. ► PDZ-GEF and Rap1 reduce endothelial junction motility.