The cytoskeleton protein vinculin helps prevent neighboring endothelial cells from separating too far, Huveneers et al. show.

Endothelial cells that line blood vessels interlock with their neighbors to form a continuous surface. These connections can become leaky during diseases such as atherosclerosis. But intercellular junctions must temporarily loosen so that white blood cells can exit the bloodstream and new vessels can grow from existing ones. Molecules such as vascular endothelial growth factor (VEGF), tumor necrosis factor α (TNFα), and thrombin spur such junctional rearrangements.

Huveneers et al. discovered that there are two kinds of junctions between endothelial cells: “mature” or stable junctions, which remain sealed; and focal adherens junctions (FAJs), which partially unzip. The two kinds of junctions show several structural differences, such as in the orientation of their associated actin fibers. VEGF, TNFα, and thrombin prompted stable junctions to convert to FAJs, a process that required the actin cytoskeleton to pull on FAJs.

Unlike stable junctions, FAJs contain the actin-binding protein vinculin. To probe its function, the researchers furnished cells with a modified version of one of vinculin's binding partners, α-catenin, thus preventing vinculin from reaching the junctions. In these cells, FAJs formed, but they opened farther than normal and took longer to reseal. Thus, vinculin's job is to limit how far cellular junctions open. Researchers might be able to harness vinculin's ability to treat conditions such as pulmonary edema, when fluid builds up in the lungs.

et al
J. Cell Biol.