Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells.
Tight junctions (TJs) in endothelial cells are thought to determine vascular permeability. Recently, claudin-1 to -15 were identified as major components of TJ strands. Among these, claudin-5 (also called transmembrane protein deleted in velo-cardio-facial syndrome [TMVCF]) was expressed ubiquitously, even in organs lacking epithelial tissues, suggesting the possible involvement of this claudin species in endothelial TJs. We then obtained a claudin-6-specific polyclonal antibody and a polyclonal antibody that recognized both claudin-5/TMVCF and claudin-6. In the brain and lung, immunofluorescence microscopy with these polyclonal antibodies showed that claudin-5/TMVCF was exclusively concentrated at cell-cell borders of endothelial cells of all segments of blood vessels, but not at those of epithelial cells. Immunoreplica electron microscopy revealed that claudin-5/TMVCF was a component of TJ strands. In contrast, in the kidney, the claudin-5/TMVCF signal was restricted to endothelial cells of arteries, but was undetectable in those of veins and capillaries. In addition, in all other tissues we examined, claudin-5/TMVCF was specifically detected in endothelial cells of some segments of blood vessels, but not in epithelial cells. Furthermore, when claudin-5/TMVCF cDNA was introduced into mouse L fibroblasts, TJ strands were reconstituted that resembled those in endothelial cells in vivo, i.e., the extracellular face-associated TJs. These findings indicated that claudin-5/TMVCF is an endothelial cell-specific component of TJ strands.
Morita
K
K
Department of Cell Biology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Sasaki
H
H
Furuse
M
M
Tsukita
S
S
D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000196:embryology; D001923:Brain Chemistry; D062507:Claudin-5; D057167:Claudins; D004622:Embryo, Mammalian / Q000098:blood supply / Q000737:chemistry / Q000166:cytology; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000196:embryology / Q000648:ultrastructure; D007422:Intestines / Q000098:blood supply / Q000737:chemistry / Q000166:cytology; D007668:Kidney / Q000098:blood supply / Q000737:chemistry / Q000166:cytology; D007739:L Cells; D008168:Lung / Q000098:blood supply / Q000737:chemistry / Q000166:cytology; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000276:immunology; D019108:Tight Junctions / Q000737:chemistry* / Q000648:ultrastructure; D014162:Transfection
D000906:Antibodies; D062507:Claudin-5; D057167:Claudins; C491511:Cldn5 protein, mouse; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C122101:claudin 6