Kidney Week

Abstract: TH-PO333

Claudin-19 Expression in the Thick Ascending Limb Is Required for Tight Junctional Localization of Claudin-16

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Basic
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders

• 1001 Fluid‚ Electrolyte‚ and Acid-Base Disorders: Basic

Authors

• Prot-Bertoye, Caroline, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, CNRS ERL 8228 - Laboratoire de Physiologie Rénale et Tubulopathies, Paris, France

Caroline Prot-Bertoye,

• Griveau, Camille, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, CNRS ERL 8228 - Laboratoire de Physiologie Rénale et Tubulopathies, Paris, France

Camille Griveau,

• Ling, Wung-Man Evelyne, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, CNRS ERL 8228 - Laboratoire de Physiologie Rénale et Tubulopathies, Paris, France

Wung-Man Evelyne Ling,

• Brideau, Gaëlle, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, CNRS ERL 8228 - Laboratoire de Physiologie Rénale et Tubulopathies, Paris, France

Gaëlle Brideau,

• Cheval, Lydie, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, CNRS ERL 8228 - Laboratoire de Physiologie Rénale et Tubulopathies, Paris, France

Lydie Cheval,

• Dimke, Henrik, Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark

Henrik Dimke,

• Houillier, Pascal, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, CNRS ERL 8228 - Laboratoire de Physiologie Rénale et Tubulopathies, Paris, France

Pascal Houillier,

Background

The kidney plays a key role in mineral homeostasis. Paracellular calcium and magnesium reabsorption in the renal thick ascending limb (TAL) involves claudin (CLDN) 16 and CLDN19: accordingly, pathogenic variants in both gene cause Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC) with severe renal calcium and magnesium wasting.
In the TAL, the expression pattern of claudins at the tight junction is mosaic: tight junctions express either CLDN16/CLDN19 or CLDN10b. CLDN16 deficiency decreases paracellular permeability to calcium and magnesium and CLDN10 deficiency decreases paracellular sodium to chloride permeability ratio. However, the function of CLDN19 in vivo remains uncertain; whether CLDN19 alters CLND16 or CLDN10 localization in vivo is unknown.

Methods

We determined the localization of CLDN19 in sections of frozen and paraffin embedded kidney from wild-type and Cldn19 deficient mice using antibodies directed against the protein and examined the role of Cldn19 deletion on CLDN16 and CLDN10 localization.

Results

CLDN19 localizes to the TAL, where it is expressed in basolateral membrane domains in the outer medulla and the cortex; its expression at the tight junction of TALs is restricted to the outer stripe of outer medulla and cortex, where it colocalizes with CLDN16. In TALs from Cldn19 deficient mice, CLDN16 is expressed in basolateral membrane domains but not at the tight junction. In contrast, Cldn19 deletion does not alter CLDN10 localization.

Conclusion

In vivo, the CLDN19 protein is required for the proper CLDN16 expression at the tight junction. This finding gives a molecular explanation to the shared renal phenotypic characteristics of FHHNC caused by either CLDN16 or CLDN19 variants.