Renal localization and function of the tight junction protein, claudin-19

Am J Physiol Renal Physiol. 2007 Jul;293(1):F166-77. doi: 10.1152/ajprenal.00087.2007. Epub 2007 Mar 27.

Abstract

Claudins form a family of transmembrane tight junction proteins that play a key role in control and selectivity of paracellular transport. Mutations in claudin-19, which is expressed in kidney, retina, and myelinated peripheral neurons, were identified in familial hypomagnesemia with hypercalciuria and nephrocalcinosis, a hereditary disease causing renal Mg(2+) and Ca(2+) wasting. Here, we studied the distribution and possible functional role of claudin-19 in the renal tubule. By immunofluorescence staining of mouse kidney, claudin-19 was found to be expressed at the tight junction of the thick ascending limb of Henle, the major site of paracellular Mg(2+) reabsorption, where it colocalized with claudin-16, as well as in the thin ascending limb. The role of claudin-19 in paracellular transport was tested by stable transfection into Madin Darby canine kidney II TetOff cells to generate inducible cell lines. Claudin-19 increased the transepithelial electrical resistance and decreased permeability to monovalent and divalent cations, while anion and urea permeability were not affected. Our data suggest that claudin-19 acts as a selective cation barrier at the tight junction. This would be consistent with its physiological role to electrically seal myelinated peripheral neurons. The normal role of claudin-19 in renal tubule function remains to be determined.

Publication types

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

MeSH terms

  • Algorithms
  • Animals
  • Blotting, Western
  • Cations / metabolism
  • Cell Line
  • Diffusion
  • Dogs
  • Electric Impedance
  • Electrophysiology
  • Fluorescent Antibody Technique
  • Kidney / metabolism*
  • Kidney / ultrastructure
  • Kidney Tubules / metabolism
  • Magnesium / metabolism
  • Membrane Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium-Potassium-Chloride Symporters / metabolism
  • Solute Carrier Family 12, Member 1
  • Tight Junctions / metabolism*

Substances

  • Cations
  • Membrane Proteins
  • Slc12a1 protein, mouse
  • Sodium-Potassium-Chloride Symporters
  • Solute Carrier Family 12, Member 1
  • Magnesium