Renal salt wasting and chronic dehydration in claudin-7-deficient mice

Tatum, Rodney; Zhang, Yuguo; Salleng, Kenneth J.; Lü, Zhe; Lin, Jen-Jar; Lü, Qun; Jeansonne, Beverly G.; Ding, Lei; Chen, Yanhua

doi:10.1152/ajprenal.00450.2009

Cited by 103 publications

(85 citation statements)

References 41 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CLDN7 KD resulted in a 30% decrease in TER but no significant change in ion selectivity (P Cl /P Na ; siRNA 772 shown as representative; Table 1), indicating a TJ barrier-function defect. This is consistent with the in vivo findings that CLDN7 KO animal kidneys lose major extracellular ions, such as Na + , K + , and Cl -, in a similar rate (14). Our findings suggest that the paracellular Clchannel in the collecting duct is formed by CLDN4 and CLDN8, without involving CLDN3 or CLDN7.…”

Section: Mutagenesis Identifies a Locus Of Amino Acids Critical For Csupporting

confidence: 92%

“…Thus, CLDN8 is required for the paracellular Cl -channel in the collecting duct. Immunofluorescence analyses have shown that CLDN3 and 7 are also expressed in the collecting ducts of mouse and rat kidneys (12,14), although one study described CLDN7 in the collecting ducts as located primarily on the basolateral membrane (13). Both M-1 and mIMCD3 cells express endogenous CLDN3 and CLDN7.…”

Section: Mutagenesis Identifies a Locus Of Amino Acids Critical For Cmentioning

confidence: 99%

“…CLDN3, 4, 7, and 8 are expressed primarily along the ASDN (12)(13)(14). In cultured renal epithelial MDCK cells, CLDN4 or CLDN8 overexpression selectively decreased the permeability of cations through TJs, specifically to Na + , K + , H + , and ammonium (15,16).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Claudin-4 forms paracellular chloride channel in the kidney and requires claudin-8 for tight junction localization

Hou

Renigunta²,

Yang³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

209

233

View full text Add to dashboard Cite

Tight junctions (TJs) play a key role in mediating paracellular ion reabsorption in the kidney. The paracellular pathway in the collecting duct of the kidney is a predominant route for transepithelial chloride reabsorption that determines the extracellular NaCl content and the blood pressure. However, the molecular mechanisms underlying the paracellular chloride reabsorption in the collecting duct are not understood. Here we showed that in mouse kidney collecting duct cells, claudin-4 functioned as a Cl -channel. A positively charged lysine residue at position 65 of claudin-4 was critical for its anion selectivity. Claudin-4 was observed to interact with claudin-8 using several criteria. In the collecting duct cells, the assembly of claudin-4 into TJ strands required its interaction with claudin-8. Depletion of claudin-8 resulted in the loss of paracellular chloride conductance, through a mechanism involving its recruitment of claudin-4 during TJ assembly. Together, our data show that claudin-4 interacts with claudin-8 and that their association is required for the anion-selective paracellular pathway in the collecting duct, suggesting a mechanism for coupling chloride reabsorption with sodium reabsorption in the collecting duct.C hloride is the predominant extracellular ionic constituent and thereby determines extracellular fluid volume (ECFV) and blood pressure (1-3). Although only responsible for the reabsorption of 2-3% filtered chloride, the aldosterone-sensitive distal nephron (ASDN) plays a vital regulatory role in renal handling of salt, ECFV control, and managing blood pressure (4). The ASDN comprises the distal convoluted tubule (DCT), the connecting tubule (CNT), and the collecting duct. The collecting duct is characterized by a heterogeneous epithelium-the principal cells and intercalated cells (5). Sodium reabsorption in the collecting duct is an active process driven by the basolateral Na + /K + -ATPase; acts through the apical epithelial sodium channel (ENaC) in the principal cell (6); and is responsible for generating the lumen-negative transepithelial potential. This electrogenic transport step creates a favorable electrical driving force for luminal reabsorption of chloride and secretion of potassium and proton. Chloride is transported by two major mechanisms (1). Chloride is actively reabsorbed by an electroneutral Cl − /HCO − exchanger (Slc26a4: pendrin) localized to the apical membrane of the β-type intercalated cell (7). Choride exits this cell via a basolateral Cl − channel (2) and diffuses passively down electrochemical gradients via the paracellular channel in the tight junction (TJ).The TJ is the most apical member of the junctional complex found in vertebrate epithelia responsible for the barrier to movement of ions and molecules between apical and basal compartments, the paracellular pathway (8). TJs are composed of three transmembrane proteins: occludin, claudins, and junctional adhesion molecule (JAM). The claudins (CLDNs) are a 28-member family of tetraspan proteins that range in m...

show abstract

Section: Mutagenesis Identifies a Locus Of Amino Acids Critical For Csupporting

confidence: 92%

Section: Mutagenesis Identifies a Locus Of Amino Acids Critical For Cmentioning

confidence: 99%

See 1 more Smart Citation

Claudin-4 forms paracellular chloride channel in the kidney and requires claudin-8 for tight junction localization

Hou

Renigunta²,

Yang³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

209

233

View full text Add to dashboard Cite

show abstract

“…45 Mice with constitutive knockout of claudin-7 die in neonatal life of renal salt wasting, dehydration, and renal failure, consistent with a role for claudin-7 in ASDN Cl 2 reabsorption. 86 Claudin-4 and -8 act as cation barriers when overexpressed MDCK cells. [87][88][89] However, knockdown experiments in M1 and IMCD3 cell lines suggest that in native collecting ducts they are more likely to function primarily as Cl 2 pores.…”

Section: Role Of Claudins In the Aldosterone-sensitive Distal Nephronmentioning

confidence: 99%

Claudins and the Kidney

2015

Journal of the American Society of Nephrology

117

100

View full text Add to dashboard Cite

Claudins are tight-junction membrane proteins that function as both pores and barriers in the paracellular pathway in epithelial cells. In the kidney, claudins determine the permeability and selectivity of different nephron segments along the renal tubule. In the proximal tubule, claudins have a role in the bulk reabsorption of salt and water. In the thick ascending limb, claudins are important for the reabsorption of calcium and magnesium and are tightly regulated by the calcium-sensing receptor. In the distal nephron, claudins need to form cation barriers and chloride pores to facilitate electrogenic sodium reabsorption and potassium and acid secretion. Aldosterone and the with-no-lysine (WNK) proteins likely regulate claudins to fine-tune distal nephron salt transport. Genetic mutations in claudin-16 and -19 cause familial hypomagnesemic hypercalciuria with nephrocalcinosis, whereas polymorphisms in claudin-14 are associated with kidney stone risk. It is likely that additional roles for claudins in the pathogenesis of other types of kidney diseases have yet to be uncovered.

show abstract

“…Crosses were established between Cldn7 C/¡ breeders 14 and kidneys from the newborn pup offspring were sectioned for histology and total nephron number assessment. Kidney sections from all of the pups including the homozygous and heterozygous mutants appeared grossly normal with no defects noted in the extent of ureteric bud branching morphogenesis or in the organization of the cortex and the medulla.…”

Section: Multiple Claudins Are Expressed During Mouse Kidney Developmentmentioning

confidence: 99%

Claudin-7, -16, and -19 during mouse kidney development

et al. 2014

Self Cite

View full text Add to dashboard Cite

Abbreviations: E, embryonic day; P, postnatal; FHHNC, familial hypomagnesaemia with hypercalciuria and nephrocalcinosis; nd, nephric duct; ub, ureteric bud; MET, mesenchymal to epithelial transition.Members of the claudin family of tight junction proteins are critical for establishing epithelial barriers and for the regulation of paracellular transport. To understand their roles during kidney development, we first performed RT-PCR analyses and determined that 23 claudin family members were expressed in embryonic day (E) 13.5 mouse kidneys. Based on their developmental expression and phenotypes in mouse models, we hypothesized that 3 claudin members could affect nephron formation during kidney development. Using whole mount in situ hybridization and immunohistochemistry, we demonstrated that Claudin-7 (Cldn7) was expressed in the nephric duct, the emerging ureteric bud, and in tubules derived from ureteric bud branching morphogenesis. In contrast, Claudin-16 (Cldn16) and Claudin-19 (Cldn19) were expressed at later stages of kidney development in immature renal tubules that become the Loop of Henle. To determine if a loss of these claudins would perturb kidney development, we examined newborn kidneys from mutant mouse models lacking Cldn7 or Cldn16. In both models, we noted no evidence for any congenital renal malformation and quantification of nephron number did not reveal a decrease in nephron number when compared to wildtype littermates. In summary, Cldn7, Cldn16, and Cldn19 are expressed in different epithelial lineages during kidney development. Mice lacking Cldn7 or Cldn16 do not have defects in de novo nephron formation, and this suggests that these claudins primarily function to regulate paracellular transport in the mature nephron.

show abstract

Renal salt wasting and chronic dehydration in claudin-7-deficient mice

Cited by 103 publications

References 41 publications

Claudin-4 forms paracellular chloride channel in the kidney and requires claudin-8 for tight junction localization

Claudin-4 forms paracellular chloride channel in the kidney and requires claudin-8 for tight junction localization

Claudins and the Kidney

Claudin-7, -16, and -19 during mouse kidney development

Contact Info

Product

Resources

About