Slc4a4

Summary

Gene Symbol: Slc4a4
Description: solute carrier family 4 (anion exchanger), member 4
Alias: AI835705, NBC, NBC1, electrogenic sodium bicarbonate cotransporter 1, Na(+)/HCO3(-) cotransporter, electrogenic sodium bicarbonate cotransporter NBCe1 variant D, pancreas sodium bicarbonate cotransporter, sodium bicarbonate cotransporter, solute carrier family 4 member 4, solute carrier family 4, sodium bicarbonate cotransporter, member 4
Species: mouse
Products:     Slc4a4

Top Publications

  1. Bachmann O, Rossmann H, Berger U, Colledge W, Ratcliff R, Evans M, et al. cAMP-mediated regulation of murine intestinal/pancreatic Na+/HCO3- cotransporter subtype pNBC1. Am J Physiol Gastrointest Liver Physiol. 2003;284:G37-45 pubmed
    ..investigated the expression, activity, and regulation by cAMP of the Na(+)-HCO(3)(-) cotransporter isoforms NBC1 and NBCn1 in isolated murine colonic crypts...
  2. Gawenis L, Bradford E, Prasad V, Lorenz J, Simpson J, Clarke L, et al. Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter. J Biol Chem. 2007;282:9042-52 pubmed
    ..secretion in the intestinal tract, null mutant (NBC1-/-) mice were prepared by targeted disruption of its gene (Slc4a4)...
  3. Abuladze N, Lee I, Newman D, Hwang J, Boorer K, Pushkin A, et al. Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter. J Biol Chem. 1998;273:17689-95 pubmed
    ..pNBC encodes a 1079-residue polypeptide that differs at the N terminus from the recently cloned human sodium bicarbonate cotransporter isolated from kidney (kNBC) (Burnham, C. E., Amlal, H., Wang, Z., Shull, G. E., and Soleimani, M...
  4. Paine M, Snead M, Wang H, Abuladze N, Pushkin A, Liu W, et al. Role of NBCe1 and AE2 in secretory ameloblasts. J Dent Res. 2008;87:391-5 pubmed
  5. Liu Y, Xu J, Wang D, Wang L, Chen L. Cloning and identification of two novel NBCe1 splice variants from mouse reproductive tract tissues: a comparative study of NCBT genes. Genomics. 2011;98:112-9 pubmed publisher
    ..examined, in the mouse reproductive tract tissues, the mRNA expression of five NCBTs as well as the five NBCe1 (Slc4a4) variants NBCe1-A through -E, of which NBCe1-D and NBCe1-E are novel...
  6. Lacruz R, Nanci A, White S, Wen X, Wang H, Zalzal S, et al. The sodium bicarbonate cotransporter (NBCe1) is essential for normal development of mouse dentition. J Biol Chem. 2010;285:24432-8 pubmed publisher
    ..Patients with mutations to the SLC4A4 gene (coding for the sodium bicarbonate cotransporter NBCe1), have pRTA, growth delay, ocular defects, and enamel abnormalities...
  7. Osis G, Handlogten M, Lee H, Hering Smith K, Huang W, Romero M, et al. Effect of NBCe1 deletion on renal citrate and 2-oxoglutarate handling. Physiol Rep. 2016;4: pubmed publisher
    The bicarbonate transporter, NBCe1 (SLC4A4), is necessary for at least two components of the proximal tubule contribution to acid-base homeostasis, filtered bicarbonate reabsorption, and ammonia metabolism...
  8. Schrödl Häußel M, Theparambil S, Deitmer J, Roussa E. Regulation of functional expression of the electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), in mouse astrocytes. Glia. 2015;63:1226-39 pubmed publisher
    The electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) is expressed in many cell types and is a major regulator of intracellular, and extracellular pH...
  9. Pushkin A, Abuladze N, Gross E, Newman D, Tatishchev S, Lee I, et al. Molecular mechanism of kNBC1-carbonic anhydrase II interaction in proximal tubule cells. J Physiol. 2004;559:55-65 pubmed
    ..recently shown that carbonic anhydrase II (CAII) binds in vitro to the C-terminus of the electrogenic sodium bicarbonate cotransporter kNBC1 (kNBC1-ct)...

More Information

Publications34

  1. Pierreux C, Poll A, Kemp C, Clotman F, Maestro M, Cordi S, et al. The transcription factor hepatocyte nuclear factor-6 controls the development of pancreatic ducts in the mouse. Gastroenterology. 2006;130:532-41 pubmed
    ..HNF-6 controls a network of genes involved in cilium formation and in hereditary polycystic diseases. Finally, HNF-6 deficiency represents a genetically defined model of pancreatic cystic disease. ..
  2. Theparambil S, Ruminot I, Schneider H, Shull G, Deitmer J. The electrogenic sodium bicarbonate cotransporter NBCe1 is a high-affinity bicarbonate carrier in cortical astrocytes. J Neurosci. 2014;34:1148-57 pubmed publisher
    The electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) is a robust regulator of intracellular H(+) and a significant base carrier in many cell types...
  3. Oehlke O, Speer J, Roussa E. Variants of the electrogenic sodium bicarbonate cotransporter 1 (NBCe1) in mouse hippocampal neurons are regulated by extracellular pH changes: evidence for a Rab8a-dependent mechanism. Int J Biochem Cell Biol. 2013;45:1427-38 pubmed publisher
  4. Terada N, Ohno N, Saitoh S, Seki G, Komada M, Suzuki T, et al. Interaction of membrane skeletal protein, protein 4.1B and p55, and sodium bicarbonate cotransporter1 in mouse renal S1-S2 proximal tubules. J Histochem Cytochem. 2007;55:1199-206 pubmed
    ..the localization of p55, a membrane-associated guanylate kinase, and the sodium bicarbonate cotransporter1 (NBC1), to the basolateral membrane domain of S1-S2 in mouse renal proximal tubules...
  5. Praetorius J, Hager H, Nielsen S, Aalkjaer C, Friis U, Ainsworth M, et al. Molecular and functional evidence for electrogenic and electroneutral Na(+)-HCO(3)(-) cotransporters in murine duodenum. Am J Physiol Gastrointest Liver Physiol. 2001;280:G332-43 pubmed
    ..Proximal duodenal epithelial cells expressed mRNA encoding two electrogenic NBC1 isoforms and the electroneutral NBCn1...
  6. Yang D, Li Q, So I, Huang C, Ando H, Mizutani A, et al. IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK kinase pathway. J Clin Invest. 2011;121:956-65 pubmed publisher
    ..and HCO(3)(-) in secretory glands is fueled by Na(+)/HCO(3)(-) cotransport mediated by basolateral solute carrier family 4 member 4 (NBCe1-B) and by Cl(-)/HCO(3)(-) exchange mediated by luminal solute carrier family 26, member 6 (..
  7. Lo Y, Yang S, Seki G, Yamada H, Horita S, Yamazaki O, et al. Severe metabolic acidosis causes early lethality in NBC1 W516X knock-in mice as a model of human isolated proximal renal tubular acidosis. Kidney Int. 2011;79:730-41 pubmed publisher
    We have identified a novel homozygous nonsense mutation (W516X) in the kidney-type electrogenic sodium bicarbonate cotransporter 1 (NBC1) in a patient with isolated proximal renal tubular acidosis (pRTA)...
  8. Fernández Moncada I, Ruminot I, Robles Maldonado D, Alegría K, Deitmer J, Barros L. Neuronal control of astrocytic respiration through a variant of the Crabtree effect. Proc Natl Acad Sci U S A. 2018;115:1623-1628 pubmed publisher
    ..Fast brain aerobic glycolysis may be interpreted as a strategy whereby neurons manipulate neighboring astrocytes to obtain oxygen, thus maximizing information processing. ..
  9. Kim Y, Yang B, Piao Z, Oh S, Kim J, Park K. Expression of Na+/HCO3- cotransporter and its role in pH regulation in mouse parotid acinar cells. Biochem Biophys Res Commun. 2003;304:593-8 pubmed
    ..However, the parotid acinar cells required DIDS, a NBC1 inhibitor, in addition to EIPA in order to block the pH(i) recovery...
  10. Yang D, Shcheynikov N, Zeng W, Ohana E, So I, Ando H, et al. IRBIT coordinates epithelial fluid and HCO3- secretion by stimulating the transporters pNBC1 and CFTR in the murine pancreatic duct. J Clin Invest. 2009;119:193-202 pubmed publisher
    ..These findings define IRBIT as a key coordinator of epithelial fluid and HCO3- secretion and may have implications to all CFTR-expressing epithelia and to cystic fibrosis...
  11. Ruminot I, Gutierrez R, Peña Münzenmayer G, Añazco C, Sotelo Hitschfeld T, Lerchundi R, et al. NBCe1 mediates the acute stimulation of astrocytic glycolysis by extracellular K+. J Neurosci. 2011;31:14264-71 pubmed publisher
    ..The glycolytic response to K(+) was absent in astrocytes from NBCe1 null mice (Slc4a4) and was blocked by functional or pharmacological inhibition of the NBCe1...
  12. Jalali R, Guo J, Zandieh Doulabi B, Bervoets T, Paine M, Boron W, et al. NBCe1 (SLC4A4) a potential pH regulator in enamel organ cells during enamel development in the mouse. Cell Tissue Res. 2014;358:433-42 pubmed publisher
    ..Mutation in SLC4A4 (coding for the sodium-bicarbonate cotransporter NBCe1) induces developmental defects in human and murine enamel...
  13. Khakipoor S, Ophoven C, Schrödl Häußel M, Feuerstein M, Heimrich B, Deitmer J, et al. TGF-β signaling directly regulates transcription and functional expression of the electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), via Smad4 in mouse astrocytes. Glia. 2017;65:1361-1375 pubmed publisher
    The electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) expressed in astrocytes regulates intracellular and extracellular pH...
  14. Alvarez B, Loiselle F, Supuran C, Schwartz G, Casey J. Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium/bicarbonate co-transporter. Biochemistry. 2003;42:12321-9 pubmed publisher
    ..Electrogenic NBC1 catalyzes HCO(3)(-) fluxes in mammalian kidney, pancreas, and heart cells...
  15. Handlogten M, Osis G, Lee H, Romero M, Verlander J, Weiner I. NBCe1 expression is required for normal renal ammonia metabolism. Am J Physiol Renal Physiol. 2015;309:F658-66 pubmed publisher
    ..addressed the role of the proximal tubule basolateral electrogenic Na(+)-coupled bicarbonate cotransporter (NBCe1; Slc4a4) in renal ammonia metabolism...
  16. Kao L, Sassani P, Azimov R, Pushkin A, Abuladze N, Peti Peterdi J, et al. Oligomeric structure and minimal functional unit of the electrogenic sodium bicarbonate cotransporter NBCe1-A. J Biol Chem. 2008;283:26782-94 pubmed publisher
    The electrogenic sodium bicarbonate cotransporter NBCe1-A mediates the basolateral absorption of sodium and bicarbonate in the proximal tubule. In this study the oligomeric state and minimal functional unit of NBCe1-A were investigated...
  17. Fagman H, Amendola E, Parrillo L, Zoppoli P, Marotta P, Scarfò M, et al. Gene expression profiling at early organogenesis reveals both common and diverse mechanisms in foregut patterning. Dev Biol. 2011;359:163-75 pubmed publisher
    ..As an initial step in this direction we describe a regulatory pathway involving the anti-apoptotic gene Bcl2 that controls cell survival in early thyroid development. ..
  18. Shirakabe K, Priori G, Yamada H, Ando H, Horita S, Fujita T, et al. IRBIT, an inositol 1,4,5-trisphosphate receptor-binding protein, specifically binds to and activates pancreas-type Na+/HCO3- cotransporter 1 (pNBC1). Proc Natl Acad Sci U S A. 2006;103:9542-7 pubmed
    ..to identify the target molecules of IRBIT, and we succeeded in identifying Na(+)/HCO(3)(-) cotransporter 1 (NBC1) as an IRBIT binding protein...
  19. Theparambil S, Deitmer J. High effective cytosolic H+ buffering in mouse cortical astrocytes attributable to fast bicarbonate transport. Glia. 2015;63:1581-94 pubmed publisher
  20. Yu H, Riederer B, Stieger N, Boron W, Shull G, Manns M, et al. Secretagogue stimulation enhances NBCe1 (electrogenic Na(+)/HCO(3)(-) cotransporter) surface expression in murine colonic crypts. Am J Physiol Gastrointest Liver Physiol. 2009;297:G1223-31 pubmed publisher
    A Na(+)/HCO(3)(-) cotransporter (NBC) is located in the basolateral membrane of the gastrointestinal epithelium, where it imports HCO(3)(-) during stimulated anion secretion...
  21. May O, Yu H, Riederer B, Manns M, Seidler U, Bachmann O. Short-term regulation of murine colonic NBCe1-B (electrogenic Na+/HCO3(-) cotransporter) membrane expression and activity by protein kinase C. PLoS ONE. 2014;9:e92275 pubmed publisher
    ..actively secretes HCO3(-), and several lines of evidence point to an important role of Na+/HCO3(-) cotransport (NBC) as a basolateral HCO3(-) import pathway...
  22. Theparambil S, Naoshin Z, Thyssen A, Deitmer J. Reversed electrogenic sodium bicarbonate cotransporter 1 is the major acid loader during recovery from cytosolic alkalosis in mouse cortical astrocytes. J Physiol. 2015;593:3533-47 pubmed publisher
    ..present study demonstrates that outwardly-directed sodium bicarbonate cotransport via electrogenic sodium bicarbonate cotransporter 1 (NBCe1) mediates the major fraction of H(+) i regulation from cytosolic alkalosis in mouse ..
  23. Turovsky E, Theparambil S, Kasymov V, Deitmer J, del Arroyo A, Ackland G, et al. Mechanisms of CO2/H+ Sensitivity of Astrocytes. J Neurosci. 2016;36:10750-10758 pubmed
    ..by Na+ entry, markedly reduced by inhibition of Na+/HCO3- cotransport (NBC) or Na+/Ca2+ exchange (NCX), and abolished in Na+-free medium or by combined NBC/..
  24. Rickmann M, Orlowski B, Heupel K, Roussa E. Distinct expression and subcellular localization patterns of Na+/HCO3- cotransporter (SLC 4A4) variants NBCe1-A and NBCe1-B in mouse brain. Neuroscience. 2007;146:1220-31 pubmed
    ..These data demonstrate for the first time distinct cellular distribution of NBCe1 NH2-terminal variants in mouse brain. NBCe1 may be involved in neuronal modulation, and pH regulation during neuronal activity. ..
  25. Wen X, Kurtz I, Paine M. Prevention of the disrupted enamel phenotype in Slc4a4-null mice using explant organ culture maintained in a living host kidney capsule. PLoS ONE. 2014;9:e97318 pubmed publisher
    b>Slc4a4-null mice are a model of proximal renal tubular acidosis (pRTA). Slc4a4 encodes the electrogenic sodium base transporter NBCe1 that is involved in transcellular base transport and pH regulation during amelogenesis...