Vascular Endothelial-Cadherin Stabilizes at Cell–Cell Junctions by Anchoring to Circumferential Actin Bundles through α- and β-Catenins in Cyclic AMP-Epac-Rap1 Signal-activated Endothelial Cells

Abstract

Vascular endothelial (VE)-cadherin is a cell-cell adhesion molecule involved in endothelial barrier function. Here, we show that initial circumferential actin bundling induced by cyclic AMP-Epac-Rap1 signal and its linkage to VE-cadherin through α- and β-catenins lead to the stabilization of VE-cadherin at cell-cell contacts.

Isoform-specific differences between Rap1A and Rap1B GTPases in the formation of endothelial cell junctions

“…23 The junctional strengthening effect of Rap1 activation has been correlated with rearrangement of the actin cytoskeleton into prominent perijunctional ring structures and loss of actin stress fibers. 6,18,20,24 As mentioned above, switching between these actin phenotypes (perijunctional vs. stress fibers), may provide a mechanism for regulating junctional dynamics.…”

“…In ECs, the association of junctions with cortical actin bundles correlates with stable, mature junctions. 5,6 Recent studies have also shown that cell-cell junctions can associate with stress fibers that insert from neighboring cells, this type of interaction is promoted by certain inflammatory signals and is thought to contribute to tension-driven opening of cell-cell junctions. 7 Of the signaling molecules recruited to EC junctions, Rho family GTPases are known to be key regulators of cytoskeletal dynamics; they participate in signaling pathways that affect cell migration, adhesion, actin cytoskeleton remodeling, 8 and cell-cell junctions.…”

Small Rho GTPase-mediated actin dynamics at endothelial adherens junctions

“…76,78,79 Noda and coworkers showed that Rap1 activity promotes the stability of cellcell junctions by reducing the mobility of VE-cadherin. 80 More specifically, they showed that active Rap1 promotes the formation of circumferential actin bundles. In turn, VE-cadherin is connected to these bundles through aand b-catenin.…”

Actin filament association at adherens junctions

“…The mobility of these PAs along the meshwork is dependent both on α-catenin and actomyosin tension, indicating connecting to actin in α-catenindependent manner (13). In endothelial cells, the actin-binding region of α-catenin is also required for VE-cadherin stabilization and accumulation to cortical actin bundles (55). PAs were disrupted in cardiac-specific α-catenin conditional knockout mice, resulting in cardiomyopathy and susceptibility to wall rupture (56).…”