Gene Symbol: Slc12a3
Description: solute carrier family 12, member 3
Alias: AI035291, NCC, NCCT, TSC, solute carrier family 12 member 3, Na-Cl symporter, thiazide-sensitive sodium-chloride cotransporter
Species: mouse
Products:     Slc12a3

Top Publications

  1. Schultheis P, Lorenz J, Meneton P, Nieman M, Riddle T, Flagella M, et al. Phenotype resembling Gitelman's syndrome in mice lacking the apical Na+-Cl- cotransporter of the distal convoluted tubule. J Biol Chem. 1998;273:29150-5 pubmed
    Mutations in the gene encoding the thiazide-sensitive Na+-Cl- cotransporter (NCC) of the distal convoluted tubule cause Gitelman's syndrome, an inherited hypokalemic alkalosis with hypomagnesemia and hypocalciuria...
  2. Kunchaparty S, Palcso M, Berkman J, Velazquez H, Desir G, Bernstein P, et al. Defective processing and expression of thiazide-sensitive Na-Cl cotransporter as a cause of Gitelman's syndrome. Am J Physiol. 1999;277:F643-9 pubmed
  3. Golbang A, Cope G, Hamad A, Murthy M, Liu C, Cuthbert A, et al. Regulation of the expression of the Na/Cl cotransporter by WNK4 and WNK1: evidence that accelerated dynamin-dependent endocytosis is not involved. Am J Physiol Renal Physiol. 2006;291:F1369-76 pubmed
    ..These proteins alter the expression of the thiazide-sensitive Na/Cl cotransporter (NCCT) in Xenopus laevis oocytes, although the details are controversial...
  4. Rozansky D, Cornwall T, Subramanya A, Rogers S, Yang Y, David L, et al. Aldosterone mediates activation of the thiazide-sensitive Na-Cl cotransporter through an SGK1 and WNK4 signaling pathway. J Clin Invest. 2009;119:2601-12 pubmed publisher
    ..these renal epithelia, aldosterone increases expression and activity of the thiazide-sensitive Na-Cl cotransporter (NCC) and the epithelial sodium channel (ENaC)...
  5. Sohara E, Rai T, Yang S, Ohta A, Naito S, Chiga M, et al. Acute insulin stimulation induces phosphorylation of the Na-Cl cotransporter in cultured distal mpkDCT cells and mouse kidney. PLoS ONE. 2011;6:e24277 pubmed publisher
    The NaCl cotransporter (NCC) is essential for sodium reabsorption at the distal convoluted tubules (DCT), and its phosphorylation increases its transport activity and apical membrane localization...
  6. Chiga M, Rai T, Yang S, Ohta A, Takizawa T, Sasaki S, et al. Dietary salt regulates the phosphorylation of OSR1/SPAK kinases and the sodium chloride cotransporter through aldosterone. Kidney Int. 2008;74:1403-9 pubmed publisher
    ..where a mutant of Wnk4 D561A was knocked in, increased phosphorylation of the sodium chloride cotransporter (NCC) was found and the transporter was concentrated on the apical membrane of the distal tubules...
  7. Hossain Khan M, Sohara E, Ohta A, Chiga M, Inoue Y, Isobe K, et al. Phosphorylation of Na-Cl cotransporter by OSR1 and SPAK kinases regulates its ubiquitination. Biochem Biophys Res Commun. 2012;425:456-61 pubmed publisher
    Na-Cl cotransporter (NCC) is phosphorylated in its amino terminus based on salt intake under the regulation of the WNK-OSR1/SPAK kinase cascade...
  8. San Cristobal P, Pacheco Alvarez D, Richardson C, Ring A, Vazquez N, Rafiqi F, et al. Angiotensin II signaling increases activity of the renal Na-Cl cotransporter through a WNK4-SPAK-dependent pathway. Proc Natl Acad Sci U S A. 2009;106:4384-9 pubmed publisher
    ..K(+) secretion by modulating the activities of renal transporters and channels, including the Na-Cl cotransporter NCC and the K(+) channel ROMK...
  9. Ohta A, Rai T, Yui N, Chiga M, Yang S, Lin S, et al. Targeted disruption of the Wnk4 gene decreases phosphorylation of Na-Cl cotransporter, increases Na excretion and lowers blood pressure. Hum Mol Genet. 2009;18:3978-86 pubmed publisher
    ..pathogenesis of pseudohypoaldosteronism type II was the activation of the OSR1/SPAK kinase-NaCl cotransporter (NCC) phosphorylation cascade by the mutant WNK4...

More Information


  1. Vallon V, Schroth J, Lang F, Kuhl D, Uchida S. Expression and phosphorylation of the Na+-Cl- cotransporter NCC in vivo is regulated by dietary salt, potassium, and SGK1. Am J Physiol Renal Physiol. 2009;297:F704-12 pubmed publisher
    The Na-Cl cotransporter NCC is expressed in the distal convoluted tubule, activated by phosphorylation, and has been implicated in renal NaCl and K(+) homeostasis...
  2. Grieshammer U, Cebrian C, Ilagan R, Meyers E, Herzlinger D, Martin G. FGF8 is required for cell survival at distinct stages of nephrogenesis and for regulation of gene expression in nascent nephrons. Development. 2005;132:3847-57 pubmed
    ..Thus, unlike other FGF family members, which regulate growth and branching morphogenesis of the collecting duct system, Fgf8 encodes a factor essential for gene regulation and cell survival at distinct steps in nephrogenesis. ..
  3. Ishizawa K, Xu N, Loffing J, Lifton R, Fujita T, Uchida S, et al. Potassium depletion stimulates Na-Cl cotransporter via phosphorylation and inactivation of the ubiquitin ligase Kelch-like 3. Biochem Biophys Res Commun. 2016;480:745-751 pubmed publisher
    ..the KLHL3 ubiquitin ligase complex is involved in the low-K+-mediated activation of Na-Cl cotransporter (NCC) in the kidney...
  4. Needham P, Mikoluk K, Dhakarwal P, Khadem S, Snyder A, Subramanya A, et al. The thiazide-sensitive NaCl cotransporter is targeted for chaperone-dependent endoplasmic reticulum-associated degradation. J Biol Chem. 2011;286:43611-21 pubmed publisher
    The thiazide-sensitive NaCl cotransporter (NCC, SLC12A3) mediates salt reabsorption in the distal nephron of the kidney and is the target of thiazide diuretics, which are commonly prescribed to treat hypertension...
  5. Nicolet Barousse L, Blanchard A, Roux C, Pietri L, Bloch Faure M, Kolta S, et al. Inactivation of the Na-Cl co-transporter (NCC) gene is associated with high BMD through both renal and bone mechanisms: analysis of patients with Gitelman syndrome and Ncc null mice. J Bone Miner Res. 2005;20:799-808 pubmed
    ..We report that patients and mice with null mutations in the thiazide-sensitive NaCl cotransporter (NCC) have higher renal tubular Ca reabsorption, higher BMD, and lower bone remodeling than controls, as well as ..
  6. Recuenco M, Ohmori T, Tanigawa S, Taguchi A, Fujimura S, Conti M, et al. Nonmuscle Myosin II Regulates the Morphogenesis of Metanephric Mesenchyme-Derived Immature Nephrons. J Am Soc Nephrol. 2015;26:1081-91 pubmed publisher
    ..Our data also suggest that Myh9 deletion in mice results in failure to maintain renal tubules but not in glomerulosclerosis. ..
  7. McWilliams T, Prescott A, Allen G, Tamjar J, Munson M, Thomson C, et al. mito-QC illuminates mitophagy and mitochondrial architecture in vivo. J Cell Biol. 2016;214:333-45 pubmed publisher
    ..mito-QC is an experimentally advantageous tool of broad relevance to cell biology researchers within both discovery-based and translational research communities. ..
  8. Zhang C, Wang L, Zhang J, Su X, Lin D, Scholl U, et al. KCNJ10 determines the expression of the apical Na-Cl cotransporter (NCC) in the early distal convoluted tubule (DCT1). Proc Natl Acad Sci U S A. 2014;111:11864-9 pubmed publisher the early distal convoluted tubule (DCT1) and determines the expression of the apical Na-Cl cotransporter (NCC) in the DCT...
  9. Voets T, Nilius B, Hoefs S, Van Der Kemp A, Droogmans G, Bindels R, et al. TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption. J Biol Chem. 2004;279:19-25 pubmed
    ..Our data indicate that TRPM6 comprises all or part of the apical Mg2+ channel of Mg2+-absorbing epithelia. ..
  10. Kosfeld A, Brand F, Weiss A, Kreuzer M, Goerk M, Martens H, et al. Mutations in the leukemia inhibitory factor receptor (LIFR) gene and Lifr deficiency cause urinary tract malformations. Hum Mol Genet. 2017;26:1716-1731 pubmed publisher
    ..3% of CAKUT patients, and provide evidence that Lifr deficiency and deactivating LIFR mutations cause highly similar anomalies of the urogenital tract in mice and humans. ..
  11. Leviel F, Hübner C, Houillier P, Morla L, El Moghrabi S, Brideau G, et al. The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice. J Clin Invest. 2010;120:1627-35 pubmed publisher actually amiloride insensitive and sensitive to thiazide diuretics, which also block the Na-Cl cotransporter (NCC) located in the distal convoluted tubule...
  12. Alshahrani S, Rapoport R, Zahedi K, Jiang M, Nieman M, Barone S, et al. The non-diuretic hypotensive effects of thiazides are enhanced during volume depletion states. PLoS ONE. 2017;12:e0181376 pubmed publisher
    ..Thiazides initially enhance diuresis via inhibition of the kidney Na+-Cl- Cotransporter (NCC)...
  13. Ohmori T, Tanigawa S, Kaku Y, Fujimura S, Nishinakamura R. Sall1 in renal stromal progenitors non-cell autonomously restricts the excessive expansion of nephron progenitors. Sci Rep. 2015;5:15676 pubmed publisher
  14. Shibata S, Rinehart J, Zhang J, Moeckel G, Castañeda Bueno M, Stiegler A, et al. Mineralocorticoid receptor phosphorylation regulates ligand binding and renal response to volume depletion and hyperkalemia. Cell Metab. 2013;18:660-71 pubmed publisher
    ..These findings reveal a mechanism regulating nuclear hormone receptor activity and implicate selective MR activation in intercalated cells in the distinct adaptive responses to volume depletion and hyperkalemia. ..
  15. Rojas Vega L, Reyes Castro L, Ramírez V, Bautista Pérez R, Rafael C, Castañeda Bueno M, et al. Ovarian hormones and prolactin increase renal NaCl cotransporter phosphorylation. Am J Physiol Renal Physiol. 2015;308:F799-808 pubmed publisher
    ..Accordingly, a dimorphic regulation of the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC) has been reported, with a higher activity in females than in males...
  16. Richardson C, Sakamoto K, de los Heros P, Deak M, Campbell D, Prescott A, et al. Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -independent pathways. J Cell Sci. 2011;124:789-800 pubmed publisher
    Ion cotransporters, such as the Na(+)/Cl(-) cotransporter (NCC), control renal salt re-absorption and are regulated by the WNK-signalling pathway, which is over-stimulated in patients suffering from Gordon's hypertension syndrome...
  17. Brooks H, Sorensen A, Terris J, Schultheis P, Lorenz J, Shull G, et al. Profiling of renal tubule Na+ transporter abundances in NHE3 and NCC null mice using targeted proteomics. J Physiol. 2001;530:359-66 pubmed
    The Na+-H+ exchanger NHE3 and the thiazide-sensitive Na+-Cl- cotransporter NCC are the major apical sodium transporters in the proximal convoluted tubule and the distal convoluted tubule of the kidney, respectively...
  18. Sakaguchi M, Sharmin S, Taguchi A, Ohmori T, Fujimura S, Abe T, et al. The phosphatase Dullard negatively regulates BMP signalling and is essential for nephron maintenance after birth. Nat Commun. 2013;4:1398 pubmed publisher
    ..Thus, Dullard keeps BMP signalling at an appropriate level, which is required for nephron maintenance in the postnatal period. ..
  19. Liu Z, Xie J, Wu T, Truong T, Auchus R, Huang C. Downregulation of NCC and NKCC2 cotransporters by kidney-specific WNK1 revealed by gene disruption and transgenic mouse models. Hum Mol Genet. 2011;20:855-66 pubmed publisher
    ..KS-WNK1 downregulates the Na(+)-Cl(-) cotransporter NCC by antagonizing the effect of full-length WNK1 when expressed in Xenopus oocytes...
  20. Lin S, Yu I, Jiang S, Lin S, Chu P, Chen A, et al. Impaired phosphorylation of Na(+)-K(+)-2Cl(-) cotransporter by oxidative stress-responsive kinase-1 deficiency manifests hypotension and Bartter-like syndrome. Proc Natl Acad Sci U S A. 2011;108:17538-43 pubmed publisher
    ..cotransporters (NKCCs), including NKCC1 and renal-specific NKCC2, and the Na(+)-Cl(-) cotransporter (NCC) play pivotal roles in the regulation of blood pressure (BP) and renal NaCl reabsorption...
  21. Sabath E, Meade P, Berkman J, de los Heros P, Moreno E, Bobadilla N, et al. Pathophysiology of functional mutations of the thiazide-sensitive Na-Cl cotransporter in Gitelman disease. Am J Physiol Renal Physiol. 2004;287:F195-203 pubmed
    Most of the missense mutations that have been described in the human SLC12A3 gene encoding the thiazide-sensitive Na(+)-Cl(-) cotransporter (TSC, NCC, or NCCT), as the cause of Gitelman disease, block TSC function by interfering with ..
  22. Loffing J, Vallon V, Loffing Cueni D, Aregger F, Richter K, Pietri L, et al. Altered renal distal tubule structure and renal Na(+) and Ca(2+) handling in a mouse model for Gitelman's syndrome. J Am Soc Nephrol. 2004;15:2276-88 pubmed
    ..recessive renal tubulopathy caused by loss-of-function mutations in the thiazide-sensitive NaCl co-transporter (NCC) of the distal convoluted tubule (DCT), is characterized by mild renal Na(+) wasting, hypocalciuria, hypomagnesemia,..
  23. Wu G, Peng J. Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation. FEBS Lett. 2013;587:1717-22 pubmed publisher
    ..KLHL3 inhibited the positive effect of WNK4 on Na(+)-Cl(-) cotransporter (NCC) by decreasing WNK4 protein abundance without decreasing that of NCC and the downstream kinase OSR1 directly...
  24. Yang S, Fang Y, Tseng M, Chu P, Yu I, Wu H, et al. Phosphorylation regulates NCC stability and transporter activity in vivo. J Am Soc Nephrol. 2013;24:1587-97 pubmed publisher
    A T60M mutation in the thiazide-sensitive sodium chloride cotransporter (NCC) is common in patients with Gitelman's syndrome (GS)...
  25. Shoda W, Nomura N, Ando F, Mori Y, Mori T, Sohara E, et al. Calcineurin inhibitors block sodium-chloride cotransporter dephosphorylation in response to high potassium intake. Kidney Int. 2017;91:402-411 pubmed publisher
    ..Moreover, the sodium-chloride cotransporter (NCC) plays an important role in blood pressure regulation and urinary potassium excretion in response to potassium ..
  26. Nagalakshmi V, Ren Q, Pugh M, Valerius M, McMahon A, Yu J. Dicer regulates the development of nephrogenic and ureteric compartments in the mammalian kidney. Kidney Int. 2011;79:317-30 pubmed publisher
    ..Furthermore, an understanding of miRNA action may provide new insights into the etiology and pathogenesis of renal cyst-based kidney disease. ..
  27. Ronzaud C, Loffing Cueni D, Hausel P, Debonneville A, Malsure S, Fowler Jaeger N, et al. Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension. J Clin Invest. 2013;123:657-65 pubmed publisher
    ..the renal outer medullary K+ channel (ROMK), and total and phosphorylated thiazide-sensitive Na+Cl- cotransporter (NCC) levels were increased in KO kidneys...
  28. Gailly P, Szutkowska M, Olinger E, Debaix H, Seghers F, Janas S, et al. P2Y2 receptor activation inhibits the expression of the sodium-chloride cotransporter NCC in distal convoluted tubule cells. Pflugers Arch. 2014;466:2035-47 pubmed publisher
    ..Previous studies suggest that this mechanism may involve the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), which plays an essential role in NaCl reabsorption in the cells lining the distal convoluted tubule (DCT)...
  29. Donnelly B, Needham P, Snyder A, Roy A, Khadem S, Brodsky J, et al. Hsp70 and Hsp90 multichaperone complexes sequentially regulate thiazide-sensitive cotransporter endoplasmic reticulum-associated degradation and biogenesis. J Biol Chem. 2013;288:13124-35 pubmed publisher
    The thiazide-sensitive NaCl cotransporter (NCC) is the primary mediator of salt reabsorption in the distal convoluted tubule and is a key determinant of the blood pressure set point...
  30. Ye X, Wang Y, Rattner A, Nathans J. Genetic mosaic analysis reveals a major role for frizzled 4 and frizzled 8 in controlling ureteric growth in the developing kidney. Development. 2011;138:1161-72 pubmed publisher
  31. Rossier B, Staub O, Hummler E. Genetic dissection of sodium and potassium transport along the aldosterone-sensitive distal nephron: importance in the control of blood pressure and hypertension. FEBS Lett. 2013;587:1929-41 pubmed publisher
    ..This will allow to design rational strategies for the treatment of hypertension and for the development of the next generation of diuretics. ..
  32. Takahashi D, Mori T, Nomura N, Khan M, Araki Y, Zeniya M, et al. WNK4 is the major WNK positively regulating NCC in the mouse kidney. Biosci Rep. 2014;34: pubmed publisher
    ..kinase)-OSR1/SPAK (oxidative stress-responsive 1/Ste20-like proline/alanine-rich kinase) cascade regulates NCC (Na-Cl co-transporter) in the DCT (distal convoluted tubules) of the kidney...
  33. Hoorn E, Walsh S, McCormick J, Fürstenberg A, Yang C, Roeschel T, et al. The calcineurin inhibitor tacrolimus activates the renal sodium chloride cotransporter to cause hypertension. Nat Med. 2011;17:1304-9 pubmed publisher
    ..hypertension, a genetic disease characterized by overactivity of the renal sodium chloride cotransporter (NCC) and caused by mutations in genes encoding WNK kinases...
  34. Pathak B, Shaughnessy J, Meneton P, Greeb J, Shull G, Jenkins N, et al. Mouse chromosomal location of three epithelial sodium channel subunit genes and an apical sodium chloride cotransporter gene. Genomics. 1996;33:124-7 pubmed
    ..These loci map to previously defined homologous regions between human and mouse chromosomes and provide additional information regarding human/mouse comparative mapping. ..
  35. Subramanya A, Liu J, Ellison D, Wade J, Welling P. WNK4 diverts the thiazide-sensitive NaCl cotransporter to the lysosome and stimulates AP-3 interaction. J Biol Chem. 2009;284:18471-80 pubmed publisher
    ..chloride reabsorption by attenuating the cell surface expression of the thiazide-sensitive NaCl cotransporter (NCC). The underlying mechanism for this effect remains poorly understood...
  36. Mugford J, Sipila P, Kobayashi A, Behringer R, McMahon A. Hoxd11 specifies a program of metanephric kidney development within the intermediate mesoderm of the mouse embryo. Dev Biol. 2008;319:396-405 pubmed publisher
    ..This program maintains tubule forming progenitors and instructs a metanephric specific pattern of nephron differentiation. ..
  37. Grimm P, Lazo Fernández Y, Delpire E, Wall S, Dorsey S, Weinman E, et al. Integrated compensatory network is activated in the absence of NCC phosphorylation. J Clin Invest. 2015;125:2136-50 pubmed publisher
    ..mice, which are unable to activate the thiazide-sensitive sodium chloride cotransporter NCC (encoded by Slc12a3)...
  38. Werth M, Walentin K, Aue A, Schönheit J, Wuebken A, Pode Shakked N, et al. The transcription factor grainyhead-like 2 regulates the molecular composition of the epithelial apical junctional complex. Development. 2010;137:3835-45 pubmed publisher
    ..Together, our data provide evidence that Grhl2 acts as a target gene-associated transcriptional activator of apical junctional complex components and, thereby, crucially participates in epithelial differentiation. ..
  39. Xu J, Barone S, Brooks M, Soleimani M. Double knockout of carbonic anhydrase II (CAII) and Na(+)-Cl(-) cotransporter (NCC) causes salt wasting and volume depletion. Cell Physiol Biochem. 2013;32:173-83 pubmed publisher
    The thiazide-sensitive Na(+)-Cl(-) cotransporter NCC and the Cl(-)/HCO3(-)exchanger pendrin are expressed on apical membranes of distal cortical nephron segments and mediate salt absorption, with pendrin working in tandem with the ..
  40. Terker A, Zhang C, McCormick J, Lazelle R, Zhang C, Meermeier N, et al. Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride. Cell Metab. 2015;21:39-50 pubmed publisher
    ..hyperkalemic hypertension (pseudohypoaldosteronism type 2), activating the thiazide-sensitive NaCl cotransporter, NCC. Here, we show that dietary potassium deficiency activates NCC, even in the setting of high salt intake, thereby ..
  41. Poulsen S, Christensen B. Long-term aldosterone administration increases renal Na+-Cl- cotransporter abundance in late distal convoluted tubule. Am J Physiol Renal Physiol. 2017;313:F756-F766 pubmed publisher
    Renal Na+-Cl- cotransporter (NCC) is expressed in early distal convoluted tubule (DCT) 1 and late DCT (DCT2)...
  42. Chung E, Deacon P, Marable S, Shin J, Park J. Notch signaling promotes nephrogenesis by downregulating Six2. Development. 2016;143:3907-3913 pubmed
    ..Our results demonstrate how cell fates of progenitors are regulated by a transcription factor governing progenitor status and by a differentiation signal in nephrogenesis. ..
  43. Qian C, Knol J, Igarashi P, Lin F, Zylstra U, Teh B, et al. Cystic renal neoplasia following conditional inactivation of apc in mouse renal tubular epithelium. J Biol Chem. 2005;280:3938-45 pubmed
    ..Our results confirm an important role for proper regulation of Wnt/beta-catenin signaling in renal development and provide evidence that dysregulation of the pathway can initiate tumorigenesis in the kidney. ..
  44. Rinehart J, Kahle K, de los Heros P, Vazquez N, Meade P, Wilson F, et al. WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis. Proc Natl Acad Sci U S A. 2005;102:16777-82 pubmed
    ..SLC12A family, we used coexpression studies in Xenopus oocytes to investigate the effect of WNK3 on NCC and NKCC2, related kidney-specific transporters that mediate apical NaCl reabsorption in the thick ascending limb ..
  45. Wang J, Sun C, Gerdes N, Liu C, Liao M, Liu J, et al. Interleukin 18 function in atherosclerosis is mediated by the interleukin 18 receptor and the Na-Cl co-transporter. Nat Med. 2015;21:820-6 pubmed publisher with IL18, we found that IL18 interacts with the Na-Cl co-transporter (NCC; also known as SLC12A3), a 12-transmembrane-domain ion transporter protein preferentially expressed in the kidney...
  46. Nijenhuis T, Vallon V, Van Der Kemp A, Loffing J, Hoenderop J, Bindels R. Enhanced passive Ca2+ reabsorption and reduced Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia. J Clin Invest. 2005;115:1651-8 pubmed
    Thiazide diuretics enhance renal Na+ excretion by blocking the Na+-Cl- cotransporter (NCC), and mutations in NCC result in Gitelman syndrome. The mechanisms underlying the accompanying hypocalciuria and hypomagnesemia remain debated...
  47. Seaayfan E, Defontaine N, Demaretz S, Zaarour N, Laghmani K. OS9 Protein Interacts with Na-K-2Cl Co-transporter (NKCC2) and Targets Its Immature Form for the Endoplasmic Reticulum-associated Degradation Pathway. J Biol Chem. 2016;291:4487-502 pubmed publisher
    ..The identification and selective modulation of ERAD components specific to NKCC2 and its disease-causing mutants might provide novel therapeutic strategies for the treatment of type I Bartter syndrome. ..
  48. Glover M, Zuber A, O Shaughnessy K. Renal and brain isoforms of WNK3 have opposite effects on NCCT expression. J Am Soc Nephrol. 2009;20:1314-22 pubmed publisher
    ..familial form of hypertension (Gordon syndrome) by increasing expression of the thiazide-sensitive co-transporter NCCT in the kidney...
  49. Verlander J, Miller R, Frank A, Royaux I, Kim Y, Weiner I. Localization of the ammonium transporter proteins RhBG and RhCG in mouse kidney. Am J Physiol Renal Physiol. 2003;284:F323-37 pubmed
    ..These findings suggest that RhBG and RhCG may play important and cell-specific roles in ammonium transport and signaling in these regions of the kidney. ..
  50. Vallon V. Regulation of the Na+-Cl- cotransporter by dietary NaCl: a role for WNKs, SPAK, OSR1, and aldosterone. Kidney Int. 2008;74:1373-5 pubmed publisher
    ..which defines an important influence of aldosterone in the phosphorylation and thus activation of the Na(+)-Cl(-) cotransporter (NCC) in response to changes in NaCl intake and implicates the involvement of SPAK/OSR1 kinases and WNKs.
  51. Fang Y, Yang S, Cheng C, Tseng M, Hsu H, Lin S. Chronic Metabolic Acidosis Activates Renal Tubular Sodium Chloride Cotransporter through Angiotension II-dependent WNK4-SPAK Phosphorylation Pathway. Sci Rep. 2016;6:18360 pubmed publisher
    The mechanism by which chronic metabolic acidosis (CMA) regulates sodium (Na(+))-chloride (Cl(-)) cotransporter (NCC) in the renal distal convoluted tubules remains unexplored...
  52. Stewart K, Gaitan Y, Shafer M, Aoudjit L, Hu D, Sharma R, et al. A Point Mutation in p190A RhoGAP Affects Ciliogenesis and Leads to Glomerulocystic Kidney Defects. PLoS Genet. 2016;12:e1005785 pubmed publisher
    ..Together, our results establish an unexpected link between Rho GTPase regulation, ciliogenesis and glomerulocystic kidney disease. ..
  53. Bonegio R, Beck L, Kahlon R, Lu W, Salant D. The fate of Notch-deficient nephrogenic progenitor cells during metanephric kidney development. Kidney Int. 2011;79:1099-112 pubmed publisher
    ..Thus, our fate mapping studies establish that the profound effect of Notch signaling on nephrogenesis is due to the specification of proximal but not distal tubules or podocytes. ..
  54. Abu Seman N, He B, Ojala J, Wan Mohamud W, Östenson C, Brismar K, et al. Genetic and biological effects of sodium-chloride cotransporter (SLC12A3) in diabetic nephropathy. Am J Nephrol. 2014;40:408-16 pubmed publisher
    b>Solute carrier family 12 member 3 (SLC12A3) encodes a sodium/chloride transporter in kidneys...
  55. Kobayashi K, Uchida S, Mizutani S, Sasaki S, Marumo F. Intrarenal and cellular localization of CLC-K2 protein in the mouse kidney. J Am Soc Nephrol. 2001;12:1327-34 pubmed
    ..These aspects of CLC-K2 localization suggest that CLC-K2 is important in Cl(-) transport in the distal nephron segments. ..
  56. Soleimani M, Barone S, Xu J, Alshahrani S, Brooks M, McCormack F, et al. Prostaglandin-E2 Mediated Increase in Calcium and Phosphate Excretion in a Mouse Model of Distal Nephron Salt Wasting. PLoS ONE. 2016;11:e0159804 pubmed publisher
    ..Pendrin/NCC double KO (pendrin/NCC-dKO) mice display severe salt wasting under basal conditions and develop profound volume ..
  57. Lalioti M, Zhang J, Volkman H, Kahle K, Hoffmann K, Toka H, et al. Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule. Nat Genet. 2006;38:1124-32 pubmed
    ..Genetic deficiency for the Na-Cl cotransporter of the DCT (NCC) reverses phenotypes seen in TgWnk4(PHAII) mice, demonstrating that the effects of the PHAII mutation are due to ..
  58. Gamba G, Miyanoshita A, Lombardi M, Lytton J, Lee W, Hediger M, et al. Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney. J Biol Chem. 1994;269:17713-22 pubmed
    ..These proteins establish a new family of Na(+)-(K+)-Cl- cotransporters. ..
  59. Hsu Y, Yang S, Cheng C, Liu S, Huang S, Chau T, et al. Thiazide-sensitive Na+ -Cl- cotransporter (NCC) gene inactivation results in increased duodenal Ca2+ absorption, enhanced osteoblast differentiation and elevated bone mineral density. J Bone Miner Res. 2015;30:116-27 pubmed publisher
    Inactivation of the thiazide-sensitive sodium chloride cotransporter (NCC) due to genetic mutations in Gitelman's syndrome (GS) or pharmacological inhibition with thiazide diuretics causes hypocalciuria and increased bone mineral density ..
  60. Blaesse P, Airaksinen M, Rivera C, Kaila K. Cation-chloride cotransporters and neuronal function. Neuron. 2009;61:820-38 pubmed publisher
    ..The rapidly expanding work on CCCs promotes our understanding of fundamental mechanisms that control brain development and functions under normal and pathophysiological conditions. ..
  61. McCormick J, Mutig K, Nelson J, Saritas T, Hoorn E, Yang C, et al. A SPAK isoform switch modulates renal salt transport and blood pressure. Cell Metab. 2011;14:352-64 pubmed publisher
    ..An emerging model suggests that bumetanide- and thiazide-sensitive NaCl transporters (NKCC2 and NCC) along these segments are phosphorylated and activated by WNK kinases, via SPAK and OSR1...
  62. Self M, Lagutin O, Bowling B, Hendrix J, Cai Y, Dressler G, et al. Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney. EMBO J. 2006;25:5214-28 pubmed
    ..We propose that in the developing kidney, Six2 activity is required for maintaining the mesenchymal progenitor population in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud...
  63. Patel Chamberlin M, Varasteh Kia M, Xu J, Barone S, Zahedi K, Soleimani M. The Role of Epithelial Sodium Channel ENaC and the Apical Cl-/HCO3- Exchanger Pendrin in Compensatory Salt Reabsorption in the Setting of Na-Cl Cotransporter (NCC) Inactivation. PLoS ONE. 2016;11:e0150918 pubmed publisher
    The absence of NCC does not cause significant salt wasting in NCC deficient mice under basal conditions...
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    The Na(+)-Cl(-) cotransporter (NCC) in the distal convoluted tubule (DCT) of the kidney is a key determinant of Na(+) balance. Disturbances in NCC function are characterized by disordered volume and blood pressure regulation...
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    ..Taken together, these data suggest that ErbB4 signaling modulates proliferation and polarization, cellular functions critical for the development of epithelial ducts in the kidney. ..
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    ..Sodium is reabsorbed in this segment through the actions of the NaCl co-transporter (NCC), which is regulated by the with-no-lysine kinases (WNKs)...
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    ..Furthermore, the composition of saliva and urine was abnormal in these mice. These results indicate that Cp2l1 expression is required for normal duct development in both the salivary gland and kidney. ..
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    ..II (Ang II) infusion and evaluated the potential mechanistic role of the thiazide-sensitive NaCl cotransporter (NCC) and the epithelial sodium channel (ENaC)...
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    The sodium chloride cotransporter (NCC) is the principal salt absorptive pathway in the mammalian distal convoluted tubule (DCT) and is the site of action of thiazide diuretics...