Integrin-dependent regulation of the endothelial barrier.

The endothelium physically separates blood from surrounding tissue and yet allows for the regulated passage of nutrients, waste, and leukocytes into and out of the circulation. Trans-endothelium flux occurs across endothelial cells (transcellular) and between endothelial cells (paracellular). Paracellular endothelial barrier function depends on the regulation of cell-cell junctions. Interestingly, a functional relationship between cell-cell junctions and cell-matrix adhesions has long been appreciated but the molecular mechanisms underpinning this relationship are not fully understood. Here we review the evidence that supports the notion that cell-matrix interactions contribute to the regulation of cell-cell junctions, focusing primarily on the important adherens junction protein VE-cadherin. In particular, we will discuss recent insights gained into how integrin signaling impacts VE-cadherin stability in adherens junctions and endothelial barrier function.