Role of Na-K-ATPase in the assembly of tight junctions.
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.
Rajasekaran
Ayyappan K
AK
Dept. of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles 90095, USA. arajasekaran@mednet.ucla.edu
Rajasekaran
Sigrid A
SA
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D004194:Disease; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D022502:Stress Fibers / Q000378:metabolism; D019108:Tight Junctions / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism*
D015820:Cadherins; D020928:Mitogen-Activated Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase