title: Platelet endothelial cell adhesion molecule-1 and vascular endothelial cadherin cooperatively regulate fibroblast growth factor-induced modulations of adherens junction functions.
abstract: Cellular adherens junctions are formed by cadherins linked to proteins of the catenin family. In endothelial cells, not only vascular endothelial cadherin but also platelet endothelial cell adhesion molecule-1 localizes into junctions and associates with beta-catenin. To explore a putative cooperation of platelet endothelial cell adhesion molecule-1 and vascular endothelial cadherin, we analyzed transfectants expressing either platelet endothelial cell adhesion (CD31 cells) or vascular endothelial cadherin (CD144 cells) or both molecules (CD31/CD144 cells), and, for comparison, human umbilical vein endothelial cells. Basic fibroblast growth factor completely dissociated vascular endothelial cadherin/beta-catenin complexes and robustly moved beta-catenin into the nucleus in CD144 cells, whereas in CD31/CD144 cells as well as in human umbilical vein endothelial cells, fibroblast growth factor only partially dissociated the junctional complex followed by a significantly reduced nuclear translocation of beta-catenin. In contrast, in CD31 cells, the subcellular distribution of beta-catenin remained unaffected by fibroblast growth factor. As a functional consequence, fibroblast growth factor induced a complete collapse of the F-actin network in CD144 cells, a limited rearrangement of F-actin fibers in CD31/CD144 cells and no F-actin rearrangement in CD31 cells. We also analyzed the effect of fibroblast growth factor-induced rearrangement of junctions on junction permeability for leukocytes: in line with our observation that vascular endothelial cadherin was required for cells to respond to fibroblast growth factor, only in CD31/CD144 cells, but not in CD31 cells, leukocyte transmigration was significantly enhanced by fibroblast growth factor. In conclusion platelet endothelial cell adhesion molecule-1 cooperates with vascular endothelial cadherin in a mutual fashion; platelet endothelial cell adhesion molecule-1 reduces and temporarily limits fibroblast growth factor-induced dissociation of vascular endothelial cadherin/beta-catenin complexes, but requires vascular endothelial cadherin to control leukocyte transmigration in dependence of fibroblast growth factor.
authors.affiliation: Department of Dermatology, Division of General Dermatology, University of Vienna Medical School, Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Halama
authors.forename: M
authors.initials: M
authors.lastname: Gröger
authors.forename: M
authors.initials: M
authors.lastname: Pillinger
authors.forename: G
authors.initials: G
authors.lastname: Staffler
authors.forename: E
authors.initials: E
authors.lastname: Prager
authors.forename: H
authors.initials: H
authors.lastname: Stockinger
authors.forename: W
authors.initials: W
authors.lastname: Holnthoner
authors.forename: S
authors.initials: S
authors.lastname: Lechleitner
authors.forename: K
authors.initials: K
authors.lastname: Wolff
authors.forename: P
authors.initials: P
authors.lastname: Petzelbauer
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects* / Q000502:physiology*; D001792:Blood Platelets / Q000737:chemistry*; D015820:Cadherins / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000097:blood* / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000737:chemistry; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D015534:Trans-Activators; D014178:Translocation, Genetic / Q000187:drug effects; D051176:beta Catenin
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D005346:Fibroblast Growth Factors