Role of Na-K-ATPase in the assembly of tight junctions

Am J Physiol Renal Physiol. 2003 Sep;285(3):F388-96. doi: 10.1152/ajprenal.00439.2002.


Na-K-ATPase, also known as the sodium pump, is a crucial enzyme that regulates intracellular sodium homeostasis in mammalian cells. In epithelial cells Na-K-ATPase function is also involved in the formation of tight junctions through RhoA GTPase and stress fibers. In this review, a new two-step model for the assembly of tight junctions is proposed: step 1, an E-cadherin-dependent formation of partial tight junction strands and of the circumferential actin ring; and step 2, active actin polymerization-dependent tethering of tight junction strands to form functional tight junctions, an event requiring normal function of Na-K-ATPase in epithelial cells. A new role for stress fibers in the assembly of tight junctions is proposed. Also, implications of Na-K-ATPase function on tight junction assembly in diseases such as cancer, ischemia, hypomagnesemia, and polycystic kidney disease are discussed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Disease
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Stress Fibers / metabolism
  • Tight Junctions / chemistry
  • Tight Junctions / enzymology*
  • Tight Junctions / metabolism*


  • Cadherins
  • Mitogen-Activated Protein Kinases
  • Sodium-Potassium-Exchanging ATPase