Interendothelial junctions and their role in the control of angiogenesis, vascular permeability and leukocyte transmigration

Endothelial cell-cell junctions play an important role in vascular hemostas is. The two junctional proteins VE-cadherin and JAM-I are localized at adhe rens and tight junctions, respectively. VE-cadherin is only expressed by en dothelial cells, suggesting that it can exert cell specific function. Absen ce of VE-cadherin or blocking of its adhesive activity prevents a normal or ganization of new vascular structures, suggesting that VE-cadherin may be a molecular target of antiangiogenic therapy. In addition, the ability of pe rmeability-increasing agents and adherent leukocytes to modify VE-cadherin/ catenin organization may be related to a role in the control of vascular pe rmeability and leukocyte infiltration. JAM-I is an integral membrane protei n expressed in endothelial and epithelial cells. Its extracellular domain c an dimerize and bind homophilically. The intracellular domain (and in parti cular a PDZ-binding motif) enables JAM-I to interact with structural and si gnaling proteins. Study of the molecular interactions of JAM-1 may help exp lain mechanisms of JAM-mediated function, such as control of paracellular p ermeability and leukocyte transmigration.