Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex

Jianghui Hou, Aparna Renigunta, Martin Konrad, Antonio S. Gomes, Eveline E. Schneeberger, David L. Paul, Siegfried Waldegger, Daniel A. Goodenough

Research output: Contribution to journalArticle

229 Scopus citations

Abstract

Tight junctions (TJs) play a key role in mediating paracellular ion reabsorption in the kidney. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an inherited disorder caused by mutations in the genes encoding the TJ proteins claudin-16 (CLDN16) and CLDN19; however, the mechanisms underlying the roles of these claudins in mediating paracellular ion reabsorption in the kidney are not understood. Here we showed that in pig kidney epithelial cells, CLDN19 functioned as a Cl? blocker, whereas CLDN16 functioned as a Na+ channel. Mutant forms of CLDN19 that are associated with FHHNC were unable to block Cl? permeation. Coexpression of CLDN16 and CLDN19 generated cation selectivity of the TJ in a synergistic manner, and CLDN16 and CLDN19 were observed to interact using several criteria. In addition, disruption of this interaction by introduction of FHHNC-causing mutant forms of either CLDN16 or CLDN19 abolished their synergistic effect. Our data show that CLDN16 interacts with CLDN19 and that their association confers a TJ with cation selectivity, suggesting a mechanism for the role of mutant forms of CLDN16 and CLDN19 in the development of FHHNC.

Original languageEnglish
Pages (from-to)619-628
Number of pages10
JournalJournal of Clinical Investigation
Volume118
Issue number2
DOIs
StatePublished - Feb 1 2008

Fingerprint Dive into the research topics of 'Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex'. Together they form a unique fingerprint.

Cite this