VE-cadherin - Function

Function

VE-cadherin is a classical cadherin from the cadherin superfamily and the gene is located in a six-cadherin cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. The encoded protein is a calcium-dependent cell–cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Functioning as a classic cadherin by imparting to cells the ability to adhere in a homophilic manner, the protein may play an important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions.

Integrity of intercellular junctions is a major determinant of permeability of the endothelium, and the VE-cadherin-based adherens junction is thought to be particularly important. VE-cadherin is known to be required for maintaining a restrictive endothelial barrier – early studies using blocking antibodies to VE-cadherin increased monolayer permeability in cultured cells and resulted in interstitial edema and hemorrhage in vivo.

VE-cadherin is indispensable for proper vascular development – there have been two transgenic mouse models of VE-cadherin deficiency, both embryonic lethal due to vascular defects. Further studies using one of these models revealed that although vasculogenesis occurred, nascent vessels collapsed or disassembled in the absence of VE-cadherin. Therefore it was concluded that VE-cadherin serves the purpose of maintaining newly formed vessels.