Structural and functional actin filament organization at cell-cell junctions in endothelial cells. In quiescent cells, junctional actin filaments can be oriented either parallel (left-hand image) or perpendicular (center image) to the cell surface. A question mark indicates that it is not known whether these two types of arrangement can interchange, or whether the perpendicular arrangement must arise de novo. Actomyosin stress fibers are anchored to the membrane through adherens junctions . VE-cadherin is required, but the stress fibers are not directly linked to the cadherin-catenin complex. They are possibly tethered to adherens junctions by afadin or other, still unidentified molecules (see Figure 2, and text for details). Subdomains with perpendicular actin fibers, called 'discontinuous adherens junctions' in , are dynamic, and undergo constant reorganization. In these areas, actin fibers of adjoining cells are connected through adherens junctions into a supercellular network . In quiescent endothelial cells, actin stress fibers are polymerized through the action of Rac and Rho, Rho signaling through the actin nucleator Dia (diaphanous-related formin) . Various stimuli activate the endothelium and induce actomyosin contraction at the dynamic domains (right-hand image), with Rho signaling through the protein kinase ROCK , and resulting in the opening of intercellular gaps, making the endothelium permeable to fluid and molecules, and facilitating the transmigration of leukocytes. In activated conditions, adherens junctions are also functionally and structurally modified (indicated by the change of the junctional symbol to blue). The molecular details of such alterations are still incompletely understood. The association of actin with adherens junctions is also likely to be modified. It remains to be defined at which molecules/structures (indicated by question marks) anchor the actin fibers at the ends that are not interacting with the adherens junction. This anchoring is critical to allow productive contraction.