Figure 4. Sema3A enhances endothelial permeability through VE-cadherin destabilization. Sema3A directly augments endothelial permeability by the mean of PlxA1 and NRP1 receptors. Further downstream signaling relies on the activation of the kinase activities bear by PI3K-γ/δ and Src. These pathways culminate at the phosphorylation and destabilization of VE-cadherin. Interestingly, in quiescent endothelial cells, VE-cadherin is associated with the phosphatase PP2A, a mechanism possibly involved in locking the adherens junctions. In this model, Src-directed PP2A phosphorylation and inactivation contribute in turn to VE-cadherin destabilization upon Sema3A challenge.