CATENIN-DEPENDENT AND CATENIN-INDEPENDENT FUNCTIONS OF VASCULAR ENDOTHELIAL CADHERIN

Vascular endothelial cadherin (VE-cadherin, cadherin-5, or 7B4) is an endothelial specific cadherin that regulates cell to cell junction org anization in this cell type, Cadherin linkage to intracellular catenin s was found to be required for their adhesive properties and for local ization at cell to cell junctions. We constructed a mutant form of VE- cadherin lacking the last 82 amino acids of the cytoplasmic domain, Su rprisingly, despite any detectable association of this truncated VE-ca dherin to catenin-cytoskeletal complex, the molecule was able to clust er at cell-cell contacts in a manner similar to wild type VE-cadherin. Truncated VE-cadherin was also able to promote calcium-dependent cell to cell aggregation and to partially inhibit cell detachment and migr ation from a confluent monolayer. In contrast, intercellular junction permeability to high molecular weight molecules was severely impaired by truncation of VE-cadherin cytoplasmic domain. These results suggest that the VE-cadherin extracellular domain is enough for early steps o f cell adhesion and recognition. However, interaction of VE-cadherin w ith the cytoskeleton is necessary to provide strength and cohesion to the junction. The data also suggest that cadherin functional regulatio n might not be identical among the members of the family.