Slc12a3

Summary

Gene Symbol: Slc12a3
Description: solute carrier family 12 member 3
Alias: NCC, TSC, solute carrier family 12 member 3, Na-Cl symporter, solute carrier family 12 (sodium/chloride transporter), member 3, solute carrier family 12 (sodium/chloride transporters), member 3, thiazide-sensitive Na-Cl cotransporter, thiazide-sensitive sodium-chloride cotransporter
Species: rat

Top Publications

  1. doi Altered renal expression of Na(+) transporters and ROMK in protein-deprived rats
    María Celeste Ruete
    IMBECU CONICET Consejo Nacional de Investigaciones Científicas y Tecnológicas, Mendoza, Argentina
    Nephron Physiol 111:p17-29. 2009
  2. pmc Expression of the sodium potassium chloride cotransporter (NKCC1) and sodium chloride cotransporter (NCC) and their effects on rat lens transparency
    K N Chee
    New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand
    Mol Vis 16:800-12. 2010
  3. ncbi Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney
    G Gamba
    Harvard Center for Study of Kidney Disease, Harvard Medical School, Boston, Massachusetts
    J Biol Chem 269:17713-22. 1994
  4. pmc Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats
    Kathryn R Walsh
    Department of Pharmacology and Experimental Therapeutics and the Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts
    Am J Physiol Regul Integr Comp Physiol 310:R115-24. 2016
  5. doi WNK3 abrogates the NEDD4-2-mediated inhibition of the renal Na+-Cl- cotransporter
    Dagmara Lagnaz
    Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland and
    Am J Physiol Renal Physiol 307:F275-86. 2014
  6. pmc Renal NCC is unchanged in the midpregnant rat and decreased in the late pregnant rat despite avid renal Na+ retention
    Crystal A West
    Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida
    Am J Physiol Renal Physiol 309:F63-70. 2015
  7. doi Ovarian hormones and prolactin increase renal NaCl cotransporter phosphorylation
    Lorena Rojas-Vega
    Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
    Am J Physiol Renal Physiol 308:F799-808. 2015
  8. pmc Phosphorylation decreases ubiquitylation of the thiazide-sensitive cotransporter NCC and subsequent clathrin-mediated endocytosis
    Lena L Rosenbaek
    From the Department of Biomedicine and Center for Interactions of Proteins in Epithelial Transport, Aarhus University, Aarhus DK 8000, Denmark
    J Biol Chem 289:13347-61. 2014
  9. pmc Enhanced phosphorylation of Na(+)-Cl- co-transporter in experimental metabolic syndrome: role of insulin
    Radko Komers
    Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, OR 97239, USA
    Clin Sci (Lond) 123:635-47. 2012
  10. doi Rare mutations in SLC12A1 and SLC12A3 protect against hypertension by reducing the activity of renal salt cotransporters
    Rocío Acuña
    Molecular Physiology Unit, Instituto Nacional de Cardiologia Ignacio Chavez, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, and Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México Tlalpan
    J Hypertens 29:475-83. 2011

Scientific Experts

  • G Capasso
  • Crystal A West
  • R Komers
  • S Bachmann
  • Jose A Riancho
  • Kosuke Akiyama
  • Gerardo Gamba
  • Norma Vazquez
  • Norma A Bobadilla
  • Monica B Sandberg
  • Patricia Meade
  • Paola de los Heros
  • Diana Pacheco-Alvarez
  • Arvid B Maunsbach
  • Kathryn R Walsh
  • Alicia A McDonough
  • Lorena Rojas-Vega
  • Dagmara Lagnaz
  • Erika Moreno
  • Lena L Rosenbaek
  • Rocío Acuña
  • K N Chee
  • K Mutig
  • Jose Ponce-Coria
  • María Celeste Ruete
  • Donna H Lee
  • Pedro San-Cristobal
  • Anne D M Riquier
  • Pedro San Cristóbal
  • Swasti Tiwari
  • Somia Faroqui
  • Ignacio Gimenez
  • Zhenrong Yu
  • Jesse Rinehart
  • Steven C Hebert
  • Hiroshi Kaneko
  • Claudia Tovar-Palacio
  • Akiko Matsuo
  • Tetsutaro Matayoshi
  • Joon W Shim
  • Sharon Turban
  • Robert S Hoover
  • Richard D Wainford
  • Jill T Kuwabara
  • María Castañeda-Bueno
  • Valérie Bernard
  • Rocio Bautista-Pérez
  • Juliette Hadchouel
  • Elena Zambrano
  • Victoria Ramirez
  • Isidora Arroyo-Garza
  • Chloe Rafael
  • Luis A Reyes-Castro
  • Nadine Binart
  • Maria Chavez-Canales
  • Alessia Spirlì
  • Juan Pablo Arroyo
  • Robert A Fenton
  • Olivier Staub
  • Federica Rizzo
  • Marleen L A Kortenoeven
  • Takwa S Aroankins
  • Anne Debonneville
  • Bruce Wyse
  • Y Taniyama
  • Penélope Ortal-Vite
  • Lilia Martínez-de-la-Maza
  • I Vorontsova
  • J Kistler
  • A Paliege
  • T Saritas
  • P J Donaldson
  • M Bleich
  • Q Shan
  • T Borowski
  • S Uchida
  • T Kahl
  • J C Lim
  • Li E Yang
  • Liliana C Carrizo
  • Patricia G Valles
  • María Victoria Bocanegra
  • Patrick K K Leong
  • Kaarina Pihakaski-Maunsbach
  • Eva Munoz
  • Hassane Amlal
  • Xinqun Hu
  • Sulaiman Sheriff
  • Yoshihisa Sugimura
  • Joseph G Verbalis

Detail Information

Publications32

  1. doi Altered renal expression of Na(+) transporters and ROMK in protein-deprived rats
    María Celeste Ruete
    IMBECU CONICET Consejo Nacional de Investigaciones Científicas y Tecnológicas, Mendoza, Argentina
    Nephron Physiol 111:p17-29. 2009
    ..The abundance of the aldosterone-regulated Na(+)-Cl(-) cotransporter (NCC) and epithelial Na(+) channel (ENaC) was higher in the LP group and was associated with higher plasma aldosterone ..
  2. pmc Expression of the sodium potassium chloride cotransporter (NKCC1) and sodium chloride cotransporter (NCC) and their effects on rat lens transparency
    K N Chee
    New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand
    Mol Vis 16:800-12. 2010
    To characterize the expression patterns of the Na+-K+-Cl(-) cotransporter (NKCC) 1 and NKCC2, and the Na+-Cl(-) cotransporter (NCC) in the rat lens and to determine if they play a role in regulating lens volume and transparency.
  3. ncbi Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney
    G Gamba
    Harvard Center for Study of Kidney Disease, Harvard Medical School, Boston, Massachusetts
    J Biol Chem 269:17713-22. 1994
    ..These proteins establish a new family of Na(+)-(K+)-Cl- cotransporters...
  4. pmc Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats
    Kathryn R Walsh
    Department of Pharmacology and Experimental Therapeutics and the Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts
    Am J Physiol Regul Integr Comp Physiol 310:R115-24. 2016
    Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension...
  5. doi WNK3 abrogates the NEDD4-2-mediated inhibition of the renal Na+-Cl- cotransporter
    Dagmara Lagnaz
    Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland and
    Am J Physiol Renal Physiol 307:F275-86. 2014
    ..WNK3 and the ubiquitin-protein ligase NEDD4-2 are key regulators of the thiazide-sensitive Na+-Cl- cotransporter (NCC), WNK3 as an activator and NEDD2-4 as an inhibitor...
  6. pmc Renal NCC is unchanged in the midpregnant rat and decreased in the late pregnant rat despite avid renal Na+ retention
    Crystal A West
    Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida
    Am J Physiol Renal Physiol 309:F63-70. 2015
    ..In the present study, we investigated the aldosterone-responsive Na(+)-Cl(-) cotransporter (NCC) in mid- and late pregnant rats compared with virgin rats...
  7. doi Ovarian hormones and prolactin increase renal NaCl cotransporter phosphorylation
    Lorena Rojas-Vega
    Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
    Am J Physiol Renal Physiol 308:F799-808. 2015
    ..Accordingly, a dimorphic regulation of the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC) has been reported, with a higher activity in females than in males...
  8. pmc Phosphorylation decreases ubiquitylation of the thiazide-sensitive cotransporter NCC and subsequent clathrin-mediated endocytosis
    Lena L Rosenbaek
    From the Department of Biomedicine and Center for Interactions of Proteins in Epithelial Transport, Aarhus University, Aarhus DK 8000, Denmark
    J Biol Chem 289:13347-61. 2014
    The thiazide-sensitive sodium chloride cotransporter, NCC, is the major NaCl transport protein in the distal convoluted tubule (DCT)...
  9. pmc Enhanced phosphorylation of Na(+)-Cl- co-transporter in experimental metabolic syndrome: role of insulin
    Radko Komers
    Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, OR 97239, USA
    Clin Sci (Lond) 123:635-47. 2012
    In the present study, we investigated the activity of the thiazide-sensitive NCC (Na(+)-Cl(-) co-transporter) in experimental metabolic syndrome and the role of insulin in NCC activation...
  10. doi Rare mutations in SLC12A1 and SLC12A3 protect against hypertension by reducing the activity of renal salt cotransporters
    Rocío Acuña
    Molecular Physiology Unit, Instituto Nacional de Cardiologia Ignacio Chavez, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, and Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México Tlalpan
    J Hypertens 29:475-83. 2011
    Screening for variants in SLC12A1 and SLC12A3 genes, encoding the renal Na:Cl (NCC) and Na:K:2Cl (NKCC2) cotransporters, respectively, in 3125 members of the Framingham Heart Study (FHS) revealed that carrying a rare mutation in one of ..
  11. ncbi Short-term stimulation of the thiazide-sensitive Na+-Cl- cotransporter by vasopressin involves phosphorylation and membrane translocation
    K Mutig
    , , , Philippstr 12, D 10115 Berlin, Germany
    Am J Physiol Renal Physiol 298:F502-9. 2010
    ..The Na(+)-Cl(-) cotransporter (NCC) of DCT is activated by luminal trafficking and phosphorylation at conserved NH(2)-terminal residues...
  12. pmc Acute hypertension provokes acute trafficking of distal tubule Na-Cl cotransporter (NCC) to subapical cytoplasmic vesicles
    Donna H Lee
    Dept of Cell and Neurobiology, Univ of Southern California Keck School of Medicine, 1333 San Pablo St, BMT 403, Los Angeles, CA 90089, USA
    Am J Physiol Renal Physiol 296:F810-8. 2009
    ..Distal convoluted tubule Na(+)-Cl(-) cotransporter (NCC) is regulated by trafficking between the apical plasma membrane (APM) and subapical cytoplasmic vesicles (SCV)...
  13. pmc WNK3 and WNK4 amino-terminal domain defines their effect on the renal Na+-Cl- cotransporter
    Pedro San-Cristobal
    Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Vasco de Quiroga No 15, Tlalpan 14000, Mexico City, Mexico
    Am J Physiol Renal Physiol 295:F1199-206. 2008
    Loss of physiological regulation of the renal thiazide-sensitive Na+-Cl- cotransporter (NCC) by mutant WNK1 or WNK4 results in pseudohypoaldosteronism type II (PHAII) characterized by arterial hypertension and hyperkalemia...
  14. doi Upregulation of apical sodium-chloride cotransporter and basolateral chloride channels is responsible for the maintenance of salt-sensitive hypertension
    Giovambattista Capasso
    Department of Internal Medicine, Chair of Nephrology, Faculty of Medicine, Second University of Napoli, Napoli, Italy
    Am J Physiol Renal Physiol 295:F556-67. 2008
    ..005) for Na+-Cl- (NCC) in distal convoluted tubules (DCT)...
  15. doi Expression of thiazide-sensitive Na+-Cl- cotransporter in the rat endolymphatic sac
    Kosuke Akiyama
    Department of Otolaryngology, Faculty of Medicine, Kagawa University, Kita gun Miki cho Ikenobe 1750 1, Kagawa 761 0793, Japan
    Biochem Biophys Res Commun 371:649-53. 2008
    ..The thiazide-sensitive Na(+), Cl(-) cotransporter (TSC) is an electroneutral cotransporter specific to the kidney that plays an important role in absorption of NaCl in ..
  16. ncbi ANG II provokes acute trafficking of distal tubule Na+-Cl(-) cotransporter to apical membrane
    Monica B Sandberg
    Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California, USA
    Am J Physiol Renal Physiol 293:F662-9. 2007
    The distal convoluted tubule (DCT) Na+-Cl(-) cotransporter (NCC), the target of thiazide diuretics, is responsible for the reabsorption of 5-10% of filtered NaCl...
  17. ncbi The Na+:Cl- cotransporter is activated and phosphorylated at the amino-terminal domain upon intracellular chloride depletion
    Diana Pacheco-Alvarez
    Molecular Physiology Unit, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónomade México, Tlalpan 14000, Mexico City, Mexico
    J Biol Chem 281:28755-63. 2006
    ..that has two major branches with inverse physiological functions and regulation: sodium-driven cotransporters (NCC and NKCC1/2) that mediate cellular Cl(-) influx are activated by phosphorylation, whereas potassium-driven ..
  18. ncbi Affinity-defining domains in the Na-Cl cotransporter: a different location for Cl- and thiazide binding
    Erika Moreno
    Molecular Physiology Unit, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México Tlalpan 14000, Mexico City, Mexico
    J Biol Chem 281:17266-75. 2006
    The thiazide-sensitive Na+-Cl- cotransporter (NCC) is the major pathway for salt reabsorption in the distal convoluted tubule, serves as a receptor for thiazide-type diuretics, and is involved in inherited diseases associated with ..
  19. ncbi Redistribution of distal tubule Na+-Cl- cotransporter (NCC) in response to a high-salt diet
    Monica B Sandberg
    Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California 90089 9142, USA
    Am J Physiol Renal Physiol 291:F503-8. 2006
    The distal convoluted tubule (DCT) apical Na(+)-Cl(-) cotransporter (NCC) is responsible for the reabsorption of 5-10% of filtered NaCl and is the target for thiazide diuretics...
  20. ncbi Metabolic acidosis has dual effects on sodium handling by rat kidney
    Somia Faroqui
    Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA
    Am J Physiol Renal Physiol 291:F322-31. 2006
    ..67 meq/l) after 5d of CMA. The protein abundance of the cortical Na-Cl cotransporter (NCC) remained unchanged at 24 h, but increased significantly (P < 0.01) after 5d of CMA...
  21. ncbi Increased renal alpha-ENaC and NCC abundance and elevated blood pressure are independent of hyperaldosteronism in vasopressin escape
    Swasti Tiwari
    Department of Medicine, and Center for Sex Differences, Bldg D, Rm 232, Georgetown University, 4000 Reservoir Rd NW, Washington, DC 20057 1412, USA
    Am J Physiol Renal Physiol 291:F49-57. 2006
    ..abundance of the alpha-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter (NCC), and the 70-kDa band of gamma-ENaC (Song J, Hu X, Khan O, Tian Y, Verbalis JG, and Ecelbarger CA...
  22. pmc WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis
    Jesse Rinehart
    Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 102:16777-82. 2005
    ..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 ..
  23. ncbi Gitelman syndrome: genetic and expression analysis of the thiazide-sensitive sodium-chloride transporter in blood cells
    Jose A Riancho
    Department Internal Medicine, Hospital U M Valdecilla, 39008 Santander, Spain
    Nephrol Dial Transplant 21:217-20. 2006
    Gitelman syndrome is caused by mutations of the SLC12A3 gene, which encodes the thiazide-sensitive NaCl transporter NCCT...
  24. ncbi Sodium retention in rats with liver cirrhosis is associated with increased renal abundance of NaCl cotransporter (NCC)
    Zhenrong Yu
    Division of Nephrology and Hypertension, University Hospital Inselspital, University of Berne, Freiburgstrasse 15, 3010, Berne, Switzerland
    Nephrol Dial Transplant 20:1833-41. 2005
    ..Liver cirrhosis is associated with enhanced renal tubular sodium retention, the mechanism of which is still debated. We hypothesized that liver cirrhosis is associated with increased expression of renal epithelial sodium transporter(s)...
  25. ncbi The thiazide-sensitive Na(+)-Cl(-) cotransporter gene, C1784T, and adrenergic receptor-beta3 gene, T727C, may be gene polymorphisms susceptible to the antihypertensive effect of thiazide diuretics
    Tetsutaro Matayoshi
    Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Japan
    Hypertens Res 27:821-33. 2004
    ..Forty-eight SNPs in 17 genes (ADD1, GNB3, TSC [SLC12A3], MLR [NR3C2], NCX1 [SLC8A1], WNK1, WNK4, AGT, ACE, AT1 [AGTR1], CYP11B2, ADRB1, ADRB2, ADRB3, ADRA1A, ADRA1B, ..
  26. ncbi G2736A polymorphism of thiazide-sensitive Na-Cl cotransporter gene predisposes to hypertension in young women
    Akiko Matsuo
    Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan
    J Hypertens 22:2123-7. 2004
    The thiazide-sensitive Na-Cl cotransporter (TSC) is located in the distal renal tubules...
  27. ncbi Chloride accumulation in mammalian olfactory sensory neurons
    Hiroshi Kaneko
    Institute for Biological Information Processing IBI 1, Forschungszentrum Julich, 52425 Julich, Germany
    J Neurosci 24:7931-8. 2004
    ..Cl(-) accumulation provides OSNs with the driving force for the depolarizing Cl(-) current that is the basis of the low-noise receptor current in these neurons...
  28. ncbi Ion and diuretic specificity of chimeric proteins between apical Na(+)-K(+)-2Cl(-) and Na(+)-Cl(-) cotransporters
    Claudia Tovar-Palacio
    Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Tlalpan 14000, Mexico City, Mexico
    Am J Physiol Renal Physiol 287:F570-7. 2004
    ..Thus NH(2)-terminal and COOH-terminal domains do not play a role in defining these properties. A similar conclusion can be suggested for the Na(+)-Cl(-) cotransporter...
  29. ncbi Regulation of NHE3, NKCC2, and NCC abundance in kidney during aldosterone escape phenomenon: role of NO
    Sharon Turban
    National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Am J Physiol Renal Physiol 285:F843-51. 2003
    ..occurs largely as a result of a marked suppression of the abundance of the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule but have also demonstrated a paradoxical increase in the protein abundance of the ..
  30. ncbi N-Glycosylation at two sites critically alters thiazide binding and activity of the rat thiazide-sensitive Na(+):Cl(-) cotransporter
    Robert S Hoover
    Molecular Physiology Unit, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
    J Am Soc Nephrol 14:271-82. 2003
    ..that the mutants displayed drastically decreased thiazide-sensitive (22)Na(+) uptake compared with wild-type NCC. Analysis of enhanced green fluorescence protein (EGFP)-tagged cotransporters demonstrated that this decrease in ..
  31. ncbi Interaction with grp58 increases activity of the thiazide-sensitive Na-Cl cotransporter
    Bruce Wyse
    Division of Nephrology, Hypertension, and Clinical Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201, USA
    Am J Physiol Renal Physiol 282:F424-30. 2002
    The thiazide-sensitive sodium-chloride cotransporter (NCC) is expressed by distal convoluted tubule cells of the mammalian kidney...
  32. ncbi Renal tubule-specific transcription and chromosomal localization of rat thiazide-sensitive Na-Cl cotransporter gene
    Y Taniyama
    Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, 1 1 Seiryo machi, Aoba ku, Sendai 980 8574, Japan
    J Biol Chem 276:26260-8. 2001
    The molecular mechanism underlying the renal expression localization of the thiazide-sensitive Na-Cl cotransporter (TSC) gene was studied. The TSC gene was localized to chromosome 19p12-14...