Renal localization and function of the tight junction protein, claudin-19.
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.
Angelow
Susanne
S
Department of Medicine, Division of Nephrology, Univesity of Southern California Keck School of Medicine, 2025 Zonal Ave., RMR 406, Los Angeles, CA 90033, USA.
El-Husseini
Randa
R
Kanzawa
Sanae A
SA
Yu
Alan S L
AS
D000465:Algorithms; D000818:Animals; D015153:Blotting, Western; D002412:Cations / Q000378:metabolism; D002460:Cell Line; D004058:Diffusion; D004285:Dogs; D017097:Electric Impedance; D004594:Electrophysiology; D005455:Fluorescent Antibody Technique; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D007684:Kidney Tubules / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D019108:Tight Junctions / Q000378:metabolism*
D002412:Cations; D008565:Membrane Proteins; C578715:Slc12a1 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D008274:Magnesium