title: Ouabain modulates ciliogenesis in epithelial cells.
abstract: The exchange of substances between higher organisms and the environment occurs across transporting epithelia whose basic features are tight junctions (TJs) that seal the intercellular space, and polarity, which enables cells to transport substances vectorially. In a previous study, we demonstrated that 10 nM ouabain modulates TJs, and we now show that it controls polarity as well. We gauge polarity through the development of a cilium at the apical domain of Madin-Darby canine kidney cells (MDCK, epithelial dog kidney). Ouabain accelerates ciliogenesis in an ERK1/2-dependent manner. Claudin-2, a molecule responsible for the Na(+) and H(2)O permeability of the TJs, is also present at the cilium, as it colocalizes and coprecipitates with acetylated α-tubulin. Ouabain modulates claudin-2 localization at the cilium through ERK1/2. Comparing wild-type and ouabain-resistant MDCK cells, we show that ouabain acts through Na(+),K(+)-ATPase. Taken together, our previous and present results support the possibility that ouabain constitutes a hormone that modulates the transporting epithelial phenotype, thereby playing a crucial role in metazoan life.
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City, DF 07300, Mexico.
authors.forename: Isabel
authors.initials: I
authors.lastname: Larre
authors.forename: Aida
authors.initials: A
authors.lastname: Castillo
authors.forename: Catalina
authors.initials: C
authors.lastname: Flores-Maldonado
authors.forename: Ruben G
authors.initials: RG
authors.lastname: Contreras
authors.forename: Ivan
authors.initials: I
authors.lastname: Galvan
authors.forename: Jesus
authors.initials: J
authors.lastname: Muñoz-Estrada
authors.forename: Marcelino
authors.initials: M
authors.lastname: Cereijido
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002450:Cell Communication; D002460:Cell Line; D049109:Cell Proliferation; D002923:Cilia / Q000378:metabolism*; D057167:Claudins / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism*; D047468:Immunoprecipitation; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010042:Ouabain / Q000737:chemistry* / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013256:Steroids / Q000378:metabolism; D019108:Tight Junctions; D013997:Time Factors
chemical_list: D015820:Cadherins; D057167:Claudins; D013256:Steroids; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase