2008
DOI: 10.1172/jci33970
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Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex

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, wh… Show more

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Cited by 217 publications
(355 citation statements)
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“…By contrast, Kausalya et al (57) found that claudin-16 modestly increased Mg 2ϩ permeability (P Mg ) without changing P Na , and Hou et al (44) found a marked increase in P Na with only a minor increase in P Mg . Similarly, while we have found that claudin-19, when expressed in MDCKII cells, decreases permeability to Na ϩ , Ca 2ϩ , and Mg 2ϩ (6), Hou et al (45) found that claudin-19 transfection into LLC-PK 1 cells reduced only Cl Ϫ permeability (P Cl ).…”
Section: Physiological Function Of Claudinsmentioning
confidence: 60%
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“…By contrast, Kausalya et al (57) found that claudin-16 modestly increased Mg 2ϩ permeability (P Mg ) without changing P Na , and Hou et al (44) found a marked increase in P Na with only a minor increase in P Mg . Similarly, while we have found that claudin-19, when expressed in MDCKII cells, decreases permeability to Na ϩ , Ca 2ϩ , and Mg 2ϩ (6), Hou et al (45) found that claudin-19 transfection into LLC-PK 1 cells reduced only Cl Ϫ permeability (P Cl ).…”
Section: Physiological Function Of Claudinsmentioning
confidence: 60%
“…Indeed, claudins-16 and -19 completely colocalize in the TALH and thin ascending limbs of Henle (6,61). Overexpression of claudin-19 alone has yielded conflicting results (6,45). However, when claudins-16 and -19 are coexpressed, they interact in a yeast two-hybrid system, suggesting that they may form heteromultimers (45).…”
Section: Role Of Claudins In Human Diseasesmentioning
confidence: 99%
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“…In the kidney, CLDN19 is also exclusive to the TAL (15). In vitro, CLDN16 and CLDN19 interact and form a cation-selective TJ paracellular channel (18). On the basis of these observations, we hypothesized that the CLDN19-deficient animals will phenocopy the CLDN16 knockdown (KD) and that CLDN16-CLDN19 interaction is a critical component of paracellular cation selectivity in the TAL.…”
mentioning
confidence: 99%
“…1,2 These genes encode the tight-junction proteins claudin-16 (paracellin-1) and claudin-19, respectively, which are important for the paracellular reabsorption of calcium and magnesium in the thick ascending limb of Henle's loop. 3 Claudin-19 is also expressed in the retinal epithelium. FHHNC is characterized by excessive urinary losses of magnesium and calcium, nephrocalcinosis, kidney stones in about 1/3 of cases and progressive renal failure.…”
Section: Mutational Spectrummentioning
confidence: 99%