Na-K-ATPase regulates tight junction permeability through occludin phosphorylation in pancreatic epithelial cells.
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.
Rajasekaran
Sigrid A
SA
Department of Pathology and Laboratory Medicine, Rm. 13-344 CHS, University of California, Los Angeles, Los Angeles, CA 90095, USA. arajasekaran@mednet.ucla.edu
Barwe
Sonali P
SP
Gopal
Jegan
J
Ryazantsev
Sergey
S
Schneeberger
Eveline E
EE
Rajasekaran
Ayyappan K
AK
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
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