Figure 1. Schematic representation of RapGEF function during different stages of barrier control. At steady-state, endothelial monolayers confer a certain level of barrier function, termed basal barrier function, during which Rap1 is continuously activated by PDZ-GEFs, possibly downstream of VE-cadherin engagement at cell–cell contacts. After induction of hyperpermeability, for instance by thrombin, barrier function is actively restored to basal levels, termed barrier recovery, during which Rap1 is activated by Src-activated C3G. High levels of barrier function (barrier tightening) are induced by cAMP via activation of the RapGEF Epac1.