title: Ca(2+)-independent cell-adhesion activity of claudins, a family of integral membrane proteins localized at tight junctions.
abstract: In multicellular organisms, various compositionally distinct fluid compartments are established by epithelial and endothelial cellular sheets. For these cells to function as barriers, tight junctions (TJs) are considered to create a primary barrier for the diffusion of solutes through the paracellular pathway [1] [2] [3]. In ultrathin sections viewed under electron microscopy, TJs appear as a series of apparent fusions, involving the outer leaflets of plasma membranes of adjacent cells, to form the so-called kissing points of TJs, where the intercellular space is completely obliterated [4]. Claudins are a family of 16 proteins whose members have been identified as major integral membrane proteins localized exclusively at TJs [5] [6] [7] [8]. It remains unclear, however, whether claudins have the cell-adhesion activity that would explain the unusual intercellular adhesion at TJs. Using mouse L-fibroblast transfectants expressing various amounts of claudin-1, -2 or -3, we found that these claudins possess Ca(2+)-independent cell-adhesion activity. Using ultrathin-section electron microscopy, we observed many kissing points of TJs between adjacent transfectants. Furthermore, the cell-adhesion activity of occludin, another integral membrane protein localized at TJs [9] [10] [11], was negligible when compared with that of claudins. Thus, claudins are responsible for TJ-specific obliteration of the intercellular space.
authors.affiliation: Department of Cell Biology Faculty of Medicine Kyoto University Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kubota
authors.forename: M
authors.initials: M
authors.lastname: Furuse
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: N
authors.initials: N
authors.lastname: Sonoda
authors.forename: K
authors.initials: K
authors.lastname: Fujita
authors.forename: A
authors.initials: A
authors.lastname: Nagafuchi
authors.forename: S
authors.initials: S
authors.lastname: Tsukita
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002449:Cell Aggregation / Q000502:physiology; D062445:Claudin-1; D062465:Claudin-3; D057167:Claudins; D007739:L Cells / Q000737:chemistry / Q000166:cytology; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008854:Microscopy, Electron; D062793:Occludin; D011993:Recombinant Fusion Proteins / Q000502:physiology; D019108:Tight Junctions / Q000737:chemistry* / Q000648:ultrastructure; D014162:Transfection
chemical_list: D062445:Claudin-1; D062465:Claudin-3; D057167:Claudins; C568113:Cldn1 protein, mouse; C113371:Cldn2 protein, mouse; C568123:Cldn3 protein, mouse; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D011993:Recombinant Fusion Proteins; D002118:Calcium