title: Enhancement of cell-cell contact by claudin-4 in renal epithelial Madin-Darby canine kidney cells.
abstract: Claudin-4 regulates ion permeability via a paracellular pathway in renal epithelial cells, but its other physiological functions have not been examined. We found that hyperosmotic stress increases claudin-4 expression in Madin-Darby canine kidney cells. Here, we examined whether claudin-4 affects cell motility, cell association, and the intracellular distribution of endogenous junctional proteins. Doxycycline-inducible expression of claudin-4 did not change endogenous levels of claudin-1, claudin-2, claudin-3, occludin, E-cadherin, and ZO-1. Claudin-4 overexpression increased cell association and decreased cell migration without affecting cell proliferation. Doxycycline did not change cell junctional protein levels, cell association or cell migration in mock-transfected cells. The insolubility of claudin-1 and -3 in Triton X-100 was increased by claudin-4 overexpression, but that of claudin-2, occludin, ZO-1, and E-cadherin was unchanged. Immunocytochemistry showed that claudin-4 overexpression increases the accumulation of claudin-1 and -3 in tight junctions (TJs). Furthermore, claudin-4 overexpression increased the association of claudin-4 with claudin-1 and -3. These results suggest that claudin-4 accumulates claudin-1 and -3 in TJs to enhance cell-cell contact in renal tubular epithelial cells.
authors.affiliation: Department of Pharmaco-Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. ikari@u-shizuoka-ken.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Ikari
authors.forename: Kosuke
authors.initials: K
authors.lastname: Atomi
authors.forename: Ayumi
authors.initials: A
authors.lastname: Takiguchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Jotaro
authors.initials: J
authors.lastname: Hirakawa
authors.forename: Junko
authors.initials: J
authors.lastname: Sugatani
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004318:Doxycycline; D017097:Electric Impedance; D004847:Epithelial Cells / Q000378:metabolism* / Q000502:physiology; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D007668:Kidney / Q000166:cytology*; D008565:Membrane Proteins / Q000378:metabolism; D009997:Osmotic Pressure; D010539:Permeability; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D012995:Solubility; D013312:Stress, Physiological; D019108:Tight Junctions / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
chemical_list: D015815:Cell Adhesion Molecules; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; D008565:Membrane Proteins; D010750:Phosphoproteins; D062826:Zonula Occludens-1 Protein; D004318:Doxycycline