IDENTIFICATION OF A NOVEL CADHERIN (VASCULAR ENDOTHELIAL CADHERIN-2) LOCATED AT INTERCELLULAR-JUNCTIONS IN ENDOTHELIAL-CELLS

Endothelial cells express two major cadherins, VE and N-cadherins, but only the former consistently participates in adherens junction organi zation. In heart microvascular endothelial cells, we identified a new member of the cadherin superfamily using polymerase chain reaction. Th e entire putative coding sequence was determined. Similarly to protoca dherins, while the extracellular domain presented homology with other members of the cadherin superfamily, the intracellular region was unre lated either to cadherins or to any other known protein. We propose fo r this new protein the name of vascular endothelial cadherin-2. By Nor thern blot analysis, the mRNA was present only in cultured endothelial cell lines but not in other cell types such as NIH 3T3, Chinese hamst er ovary, or L cells. In addition, mRNA was particularly abundant in h ighly vascularized organs such as lung or kidney. In endothelial cells and transfectants, this cadherin was unable to bind catenins and pres ented a weak association with the cytoskeleton, This new molecule shar es some functional properties with VE-cadherin and other members of th e cadherin family. In Chinese hamster ovary transfectants it promoted homotypic Ca2+ dependent aggregation and adhesion and clustered at int ercellular junctions. How ever, in contrast to VE-cadherin, it did not modify paracellular permeability, cell migration, and density-depende nt cell growth. These observations suggest that different cadherins ma y promote hemophilic cell-to cell adhesion but that the functional con sequences of this interaction depend on their binding to specific intr acellular signaling/cytoskeletal proteins.