Na-K-ATPase regulates tight junction permeability through occludin phosphorylation in pancreatic epithelial cells

Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G124-33. doi: 10.1152/ajpgi.00297.2006. Epub 2006 Sep 7.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cadherins / metabolism
  • Cell Line
  • Enzyme Inhibitors / pharmacology
  • Epithelial Cells / physiology*
  • Freeze Fracturing
  • Humans
  • Membrane Proteins / metabolism*
  • Microscopy, Confocal
  • Microscopy, Immunoelectron
  • Occludin
  • Pancreas / cytology*
  • Pancreas / physiology*
  • Pancreas / ultrastructure
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Sodium-Potassium-Exchanging ATPase / drug effects
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Tight Junctions / drug effects
  • Tight Junctions / physiology*
  • Tight Junctions / ultrastructure
  • Zonula Occludens-1 Protein


  • Cadherins
  • Enzyme Inhibitors
  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • Phosphoproteins
  • TJP1 protein, human
  • Zonula Occludens-1 Protein
  • Sodium-Potassium-Exchanging ATPase