Ando et al. reveal a molecular pathway that tightens the junctions between endothelial cells.
Endothelial junctions must be flexible. To allow white blood cells to exit from a capillary, for example, endothelial cells need to loosen the connections between them. Two types of junctions in endothelial layers provide this adaptability. Zonula adherens are tighter, stable connections that are strengthened by clusters of actin fibers, called circumferential actin bundles (CABs), that run alongside the junctions. Smaller punctate junctions are looser and are bolstered by radial stress fibers that run perpendicular to the junctions. The GTPase Rap1 spurs the formation of CABs, but researchers weren’t sure how.
Ando et al. discovered that Rap1 spurs CAB formation by stimulating non-muscle myosin II. One way to activate this myosin is through the Rho-ROCK pathway, but the team found that this pathway triggers formation of radial stress fibers, not CABs. Instead, Rap1 activates the kinase MRCK to switch on myosin II at cell junctions.
The researchers then teased out more details of this pathway. Rap1 turns on Cdc42 and directs it to the cell–cell contacts. In turn, Cdc42 draws MRCK to the junctions. Rap1 also inhibits the Rho-ROCK pathway, preventing it from turning on myosin II in the cytoplasm and inducing radial stress fibers. Activating Rap1 solidified connections between cultured endothelial cells, suggesting that the pathway spurs formation of zonula adherens.
Text by Mitch Leslie