title: Na-K-ATPase regulates tight junction permeability through occludin phosphorylation in pancreatic epithelial cells.
abstract: Tight junctions are crucial for maintaining the polarity and vectorial transport functions of epithelial cells. We and others have shown that Na-K-ATPase plays a key role in the organization and permeability of tight junctions in mammalian cells and analogous septate junctions in Drosophila. However, the mechanism by which Na-K-ATPase modulates tight junctions is not known. In this study, using a well-differentiated human pancreatic epithelial cell line HPAF-II, we demonstrate that Na-K-ATPase is present at the apical junctions and forms a complex with protein phosphatase-2A, a protein known to be present at tight junctions. Inhibition of Na-K-ATPase ion transport function reduced protein phosphatase-2A activity, hyperphosphorylated occludin, induced rearrangement of tight junction strands, and increased permeability of tight junctions to ionic and nonionic solutes. These data suggest that Na-K-ATPase is required for controlling the tight junction gate function.
authors.affiliation: Department of Pathology and Laboratory Medicine, Rm. 13-344 CHS, University of California, Los Angeles, Los Angeles, CA 90095, USA. arajasekaran@mednet.ucla.edu
authors.forename: Sigrid A
authors.initials: SA
authors.lastname: Rajasekaran
authors.forename: Sonali P
authors.initials: SP
authors.lastname: Barwe
authors.forename: Jegan
authors.initials: J
authors.lastname: Gopal
authors.forename: Sergey
authors.initials: S
authors.lastname: Ryazantsev
authors.forename: Eveline E
authors.initials: EE
authors.lastname: Schneeberger
authors.forename: Ayyappan K
authors.initials: AK
authors.lastname: Rajasekaran
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000502:physiology*; D005614:Freeze Fracturing; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D062793:Occludin; D010179:Pancreas / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D062826:Zonula Occludens-1 Protein
chemical_list: D015820:Cadherins; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D000254:Sodium-Potassium-Exchanging ATPase