Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

NBCe1 Electrogenic Na+-Coupled HCO3(CO32−) Transporter

Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101572


Historical Background: SLC4 Gene Transporter Family

The NBCe1 transporter belongs to the SLC4 gene family whose 10 members are homologous membrane transport proteins that differ in their ability to transport Na+, Cl, HCO3(CO32−), H+, NH3, and water (Kurtz 2013; Parker and Boron 2013; Liu et al. 2015). AE1, AE2, and AE3 (SLC4A1, −2, −3, respectively) mediate the electroneutral exchange of Cl and HCO3. The SLC4A9 gene encodes AE4 has previously been reported to function as a Cl/HCO3 exchanger and electroneutral Na+-HCO3 cotransporter, but has recently been shown to mediate electroneutral monovalent cation (Na+/K+)-dependent Cl/HCO3 exchange (Pena-Munzenmayer et al. 2016). NDCBE (encoded by SLC4A8) like AE1, AE2, and AE3 is an anion exchanger yet differs in that it couples the electroneutral transport of Na+ and HCO3 (or CO32−) in exchange for Cl. NBCn1 (SLC4A7 gene) and NBCn2 (SLC4A10 gene) transport Na+-HCO3...
This is a preview of subscription content, log in to check access.



Dr. Kurtz is supported in part by funds from the NIH (R01-DK077162), the Allan Smidt Charitable Fund, the Factor Family Foundation Chair in Nephrology, and the Arvey Foundation.


  1. Abdulnour-Nakhoul S, Nakhoul HN, Kalliny MI, Gyftopoulos A, Rabon E, Doetjes R, et al. Ion transport mechanisms linked to bicarbonate secretion in the esophageal submucosal glands. Am J Phys Regul Integr Comp Phys. 2011;301:R83–96.Google Scholar
  2. 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. 1998a;273:17689–95.CrossRefPubMedGoogle Scholar
  3. Abuladze N, Lee I, Newman D, Hwang J, Pushkin A, Kurtz I. Axial heterogeneity of sodium-bicarbonate cotransporter expression in the rabbit proximal tubule. Am J Physiol. 1998b;274:F628–33.PubMedGoogle Scholar
  4. Abuladze N, Song M, Pushkin A, Newman D, Lee I, Nicholas S, et al. Structural organization of the human NBC1 gene: kNBC1 is transcribed from an alternative promoter in intron 3. Gene. 2000;251:109–22.CrossRefPubMedGoogle Scholar
  5. Abuladze N, Azimov R, Newman D, Sassani P, Liu W, Tatishchev S, et al. Critical amino acid residues involved in the electrogenic sodium-bicarbonate cotransporter kNBC1-mediated transport. J Physiol. 2005;565:717–30.  https://doi.org/10.1113/jphysiol.2005.084988.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Alvarez BV, Loiselle FB, Supuran CT, Schwartz GJ, Casey JR. Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium/bicarbonate co-transporter. Biochemistry. 2003;42:12321–9.  https://doi.org/10.1021/bi0353124.CrossRefPubMedGoogle Scholar
  7. Amlal H, Habo K, Soleimani M. Potassium deprivation upregulates expression of renal basolateral Na+-HCO3 cotransporter (NBC-1). Am J Phys Renal Phys. 2000;279:F532–43.Google Scholar
  8. Amlal H, Chen Q, Greeley T, Pavelic L, Soleimani M. Coordinated down-regulation of NBC-1 and NHE-3 in sodium and bicarbonate loading. Kidney Int. 2001;60:1824–36.CrossRefPubMedGoogle Scholar
  9. Ando H, Mizutani A, Matsu-ura T, Mikoshiba K. IRBIT, a novel inositol 1,4,5-trisphosphate (IP3) receptor-binding protein, is released from the IP3 receptor upon IP3 binding to the receptor. J Biol Chem. 2003;278:10602–10612.CrossRefPubMedGoogle Scholar
  10. Ando H, Kawaai K, Mikoshiba K. IRBIT: a regulator of ion channels and ion transporters. Biochim. Biophys Acta. 2014;1843:2195–2204.CrossRefPubMedGoogle Scholar
  11. Ando H, Hirose M, Gainche L, Kawaai K, Bonneau B, Ijuin T, et al. IRBIT Interacts with the catalytic core of phosphatidylinositol phosphate kinase type Iα and IIα through conserved catalytic aspartate residues. PLoS One. 2015;10:e0141569.  https://doi.org/10.1371/journal.pone.0141569.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Arakawa T, Kobayashi-Yurugi T, Alguel Y, Iwanari H, Hatae H, Iwata M, et al. Crystal structure of the anion exchanger domain of human erythrocyte band 3. Science. 2015;350:680–4.  https://doi.org/10.1126/science.aaa4335.CrossRefPubMedGoogle Scholar
  13. Azimov R, Abuladze N, Sassani P, Newman D, Kao L, Liu W, et al. G418-mediated ribosomal read-through of a nonsense mutation causing autosomal recessive proximal renal tubular acidosis. Am J Physiol Ren Physiol. 2008;295:F633–41.CrossRefGoogle Scholar
  14. Bachmann O, Rossmann H, Berger UV, Colledge WH, Ratcliff R, Evans MJ, et al. cAMP-mediated regulation of murine intestinal/pancreatic Na+/HCO3 cotransporter subtype pNBC1. Am J Physiol Gastrointest Liver Physiol. 2003;284:G37–45.CrossRefPubMedGoogle Scholar
  15. Bae JS, Koo NY, Namkoong E, Davies AJ, Choi SK, Shin Y, et al. Chaperone stress 70 protein (STCH) binds and regulates two acid/base transporters NBCe1-B and NHE1. J Biol Chem. 2013;288:6295–305.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Bartolo RC, Harfoot N, Gill M, McLeod BJ, Butt AG. Secretagogues stimulate electrogenic HCO3 secretion in the ileum of the brushtail possum, Trichosurus vulpecula: evidence for the role of a Na+/HCO3 cotransporter. J Exp Biol. 2009;212:2645–55.CrossRefPubMedGoogle Scholar
  17. Batlle D, Haque SK. Genetic causes and mechanisms of distal renal tubular acidosis. Nephrol Dial Transplant. 2012;27:3691–704.CrossRefPubMedGoogle Scholar
  18. Becker HM, Deitmer JW. Carbonic anhydrase II increases the activity of the human electrogenic Na+/HCO3 cotransporter. J Biol Chem. 2007;282:13508–21.CrossRefPubMedGoogle Scholar
  19. Bok D, Schibler MJ, Pushkin A, Sassani P, Abuladze N, Naser Z, et al. Immunolocalization of electrogenic sodium-bicarbonate cotransporters pNBC1 and kNBC1 in the rat eye. Am J Phys Renal Phys. 2001;281:F920–35.Google Scholar
  20. Boron WF. Acid-base transport by the renal proximal tubule. J Am Soc Nephrol. 2006;17:2368–82.PubMedCrossRefGoogle Scholar
  21. Boron WF, Boulpaep EL. Intracellular pH regulation in the renal proximal tubule of the salamander. Basolateral HCO3- transport. J General Physiol. 1983;81:53–94.CrossRefGoogle Scholar
  22. Bosley TM, Salih MA, Alorainy IA, Islam MZ, Oystreck DT, Suliman OS, et al. The neurology of carbonic anhydrase type II deficiency syndrome. Brain. 2011;134:3502–15.CrossRefPubMedGoogle Scholar
  23. Brandes A, Oehlke O, Schumann A, Heidrich S, Thevenod F, Roussa E. Adaptive redistribution of NBCe1-A and NBCe1-B in rat kidney proximal tubule and striated ducts of salivary glands during acid-base disturbances. Am J Physiol Regul Integr Comp Physiol. 2007;293:R2400–11.CrossRefPubMedGoogle Scholar
  24. Brenes LG, Brenes JN, Hernandez MM. Familial proximal renal tubular acidosis. A distinct clinical entity. Am J Med. 1977;63:244–52.CrossRefPubMedGoogle Scholar
  25. Capasso G, Jaeger P, Giebisch G, Guckian V, Malnic G. Renal bicarbonate reabsorption in the rat. II. Distal tubule load dependence and effect of hypokalemia. J Clin Invest. 1987;80:409–14.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Chang MH, DiPiero J, Sonnichsen FD, Romero MF. Entry to “formula tunnel” revealed by SLC4A4 human mutation and structural model. J Biol Chem. 2008;283:18402–10.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Chang MH, Chen AP, Romero MF. NBCe1A dimer assemble visualized by bimolecular fluorescence complementation. Am J Phys Renal Phys. 2014;306:F672–80.  https://doi.org/10.1152/ajprenal.00284.2013.CrossRefGoogle Scholar
  28. Chen LM, Liu Y, Boron WF. Role of an extracellular loop in determining the stoichiometry of Na+-HCO3 cotransporters. J Physiol. 2011;589:877–90.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Chen LM, Qin X, Moss FJ, Liu Y, Boron WF. Effect of simultaneously replacing putative TM6 and TM12 of human NBCe1-A with those from NBCn1 on surface abundance in Xenopus oocytes. J Membrane Miol. 2012;245:131–40.CrossRefGoogle Scholar
  30. Ch’en FF, Villafuerte FC, Swietach P, Cobden PM, Vaughan-Jones RD. S0859, an N-cyanosulphonamide inhibitor of sodium-bicarbonate cotransport in the heart. Br J Pharmacol. 2008;153:972–82.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Choi I, Romero MF, Khandoudi N, Bril A, Boron WF. Cloning and characterization of a human electrogenic Na+-HCO3 cotransporter isoform (hhNBC). Am J Phys Anthropol. 1999;276:C576–84.Google Scholar
  32. Choi I, Hu L, Rojas JD, Schmitt BM, Boron WF. Role of glycosylation in the renal electrogenic Na+-HCO3 cotransporter (NBCe1). Am J Phys Renal Phys. 2003;284:F1199–206.Google Scholar
  33. Coppola S, Frömter E. An electrophysiological study of angiotensin II regulation of Na-HCO3 cotransport and K conductance in renal proximal tubules. I. Effect of picomolar concentrations. Pflugers Arch. 1994a;427:143–50.CrossRefPubMedGoogle Scholar
  34. Coppola S, Frömter E. An electrophysiological study of angiotensin II regulation of Na-HCO3 cotransport and K conductance in renal proximal tubules. II. Effect of micromolar concentrations. Pflugers Arch. 1994b;427:151–6.CrossRefPubMedGoogle Scholar
  35. De Giusti VC, Orlowski A, Villa-Abrille MC, de Cingolani GE, Casey JR, Alvarez BV, et al. Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools. Br J Pharmacol. 2011;164:1976–89.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Deda G, Ekim M, Guven A, Karagol U, Tumer N. Hypopotassemic paralysis: a rare presentation of proximal renal tubular acidosis. J Child Neurol. 2001;16:770–1.CrossRefPubMedGoogle Scholar
  37. Demirci FY, Chang MH, Mah TS, Romero MF, Gorin MB. Proximal renal tubular acidosis and ocular pathology: a novel missense mutation in the gene (SLC4A4) for sodium bicarbonate cotransporter protein (NBCe1). Mol Vis. 2006;12:324–30.PubMedGoogle Scholar
  38. Devogelaere B, Beullens M, Sammels E, Derua R, Waelkens E, van Lint J. Protein phosphatase-1 is a novel regulator of the interaction between IRBIT and the inositol 1,4,5-trisphosphate receptor. Biochem J. 2007;407:303–311.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Dinour D, Chang MH, Satoh J, Smith BL, Angle N, Knecht A, et al. A novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through ion transport defects. J Biol Chem. 2004;279:52238–46.CrossRefPubMedGoogle Scholar
  40. Ducoudret O, Diakov A, Müller-Berger S, Romero MF, Frömter E. The renal Na-HCO3-cotransporter expressed in Xenopus laevis oocytes: inhibition by tenidap and benzamil and effect of temperature on transport rate and stoichiometry. Pflugers Arch. 2001;442:709–17.CrossRefPubMedGoogle Scholar
  41. Fang YW, Yang SS, Chau T, Nakamura M, Yamazaki O, Seki G, et al. Therapeutic effect of prenatal alkalization and PTC124 in Na+/HCO3 cotransporter 1 p.W516* knock-in mice. Gene Ther. 2015;22:374–81.  https://doi.org/10.1038/gt.2015.7.CrossRefPubMedGoogle Scholar
  42. Fujinaga J, Loiselle FB, Casey JR. Transport activity of chimaeric AE2-AE3 chloride/bicarbonate anion exchange proteins. Biochem J. 2003;371:687–96.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Garciarena CD, Ma YL, Swietach P, Huc L, Vaughan-Jones RD. Sarcolemmal localisation of Na+/H+ exchange and Na+-HCO3 co-transport influences the spatial regulation of intracellular pH in rat ventricular myocytes. J Physiol. 2013;591:2287–306.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Gawenis LR, Bradford EM, Prasad V, Lorenz JN, Simpson JE, Clarke LL, et al. Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3 cotransporter. J Biol Chem. 2007;282:9042–52.CrossRefPubMedGoogle Scholar
  45. Gill HS. pH-sensitive self-associations of the N-terminal domain of NBCe1-A suggest a compact conformation under acidic intracellular conditions. Protein Pept Lett. 2012;19:1054–63.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Gill HS, Choi KY, Kammili L, Popratiloff A. Rescue of the temperature-sensitive, autosomal-recessive mutation R298S in the sodium-bicarbonate cotransporter NBCe1-A characterized by a weakened dimer and abnormal aggregation. Biochim Biophys Acta. 2015;1850:1286–96.  https://doi.org/10.1016/j.bbagen.2015.02.014.CrossRefPubMedPubMedCentralGoogle Scholar
  47. Gross E, Abuladze N, Pushkin A, Kurtz I, Cotton CU. The stoichiometry of the electrogenic sodium bicarbonate cotransporter pNBC1 in mouse pancreatic duct cells is 2 HCO3:1 Na+. J Physiol. 2001a;531:375–82.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Gross E, Hawkins K, Abuladze N, Pushkin A, Cotton CU, Hopfer U, et al. The stoichiometry of the electrogenic sodium bicarbonate cotransporter NBC1 is cell-type dependent. J Physiol. 2001b;531:597–603.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Gross E, Hawkins K, Pushkin A, Sassani P, Dukkipati R, Abuladze N, et al. Phosphorylation of Ser982 in the sodium bicarbonate cotransporter kNBC1 shifts the HCO3:Na+ stoichiometry from 3:1 to 2:1 in murine proximal tubule cells. J Physiol. 2001c;537:659–65.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Gross E, Pushkin A, Abuladze N, Fedotoff O, Kurtz I. Regulation of the sodium bicarbonate cotransporter kNBC1 function: role of Asp986, Asp988 and kNBC1-carbonic anhydrase II binding. J Physiol. 2002;544:679–85.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Gross E, Fedotoff O, Pushkin A, Abuladze N, Newman D, Kurtz I. Phosphorylation-induced modulation of pNBC1 function: distinct roles for the amino- and carboxy-termini. J Physiol. 2003;549:673–82.  https://doi.org/10.1113/jphysiol.2003.042226.CrossRefPubMedPubMedCentralGoogle Scholar
  52. Hamm LL, Alperin RJ, Preisig PA. Cellular mechanisms of unrinary acidification. In: Alperin RJ, Caplan M, Moe OW, editors. Seldin and Giebisch’s the kidney: physiology and pathophysiology. Amsterdam/Boston: Elsevier/Academic; 2013. p. 1917–78.CrossRefGoogle Scholar
  53. Handlogten ME, Osis G, Lee HW, Romero MF, Verlander JW, Weiner ID. NBCe1 expression is required for normal renal ammonia metabolism. Am J Phys Renal Phys. 2015;309:F658–66.  https://doi.org/10.1152/ajprenal.00219.2015.CrossRefGoogle Scholar
  54. Haque SK, Ariceta G, Batlle D. Proximal renal tubular acidosis: a not so rare disorder of multiple etiologies. Nephrol Dial Transplant. 2012;27:4273–87.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Heyer M, Müller-Berger S, Romero MF, Boron WF, Frömter E. Stoichiometry of the rat kidney Na+-HCO3 cotransporter expressed in Xenopus laevis oocytes. Pflugers Arch. 1999;438:322–9.CrossRefPubMedGoogle Scholar
  56. Hong JH, Yang D, Shcheynikov N, Ohana E, Shin DM, Muallem S. Convergence of IRBIT, phosphatidylinositol (4,5) bisphosphate, and WNK/SPAK kinases in regulation of the Na+-HCO3 cotransporters family. Proc Natl Acad Sci USA. 2013;110:4105–10.  https://doi.org/10.1073/pnas.1221410110.CrossRefPubMedPubMedCentralGoogle Scholar
  57. Horita S, Zheng Y, Hara C, Yamada H, Kunimi M, Taniguchi S, et al. Biphasic regulation of Na+-HCO3 cotransporter by angiotensin II type 1A receptor. Hypertension. 2002;40:707–12.CrossRefPubMedGoogle Scholar
  58. Horita S, Yamada H, Inatomi J, Moriyama N, Sekine T, Igarashi T, et al. Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities. J Am Soc Nephrol. 2005;16:2270–8.CrossRefPubMedGoogle Scholar
  59. Igarashi T, Ishii T, Watanabe K, Hayakawa H, Horio K, Sone Y, et al. Persistent isolated proximal renal tubular acidosis-a systemic disease with a distinct clinical entity. Pediatr Nephrol. 1994;8:70–1.CrossRefPubMedGoogle Scholar
  60. Igarashi T, Inatomi J, Sekine T, Cha SH, Kanai Y, Kunimi M, et al. Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities. Nat Genet. 1999;23:264–6.CrossRefPubMedGoogle Scholar
  61. Igarashi T, Inatomi J, Sekine T, Seki G, Shimadzu M, Tozawa F, et al. Novel nonsense mutation in the Na+/HCO3 cotransporter gene (SLC4A4) in a patient with permanent isolated proximal renal tubular acidosis and bilateral glaucoma. J Am Soc Nephrol. 2001;12:713–8.PubMedGoogle Scholar
  62. Ishiguro H, Steward MC, Lindsay AR, Case RM. Accumulation of intracellular HCO3 by Na+-HCO3 cotransport in interlobular ducts from guinea-pig pancreas. J Physiol. 1996a;495(Pt 1):169–78.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Ishiguro H, Steward MC, Wilson RW, Case RM. Bicarbonate secretion in interlobular ducts from guinea-pig pancreas. J Physiol. 1996b;495(Pt 1):179–91.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Jalali R, Guo J, Zandieh-Doulabi B, Bervoets TJ, Paine ML, Boron WF, 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.  https://doi.org/10.1007/s00441-014-1935-4.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  66. Kao L, Azimov R, Shao XM, Frausto RF, Abuladze N, Newman D, et al. Multifunctional ion transport properties of human SLC4A11: comparison of the SLC4A11-B and SLC4A11-C variants. Am J Physiol Cell Physiol. 2016;311(5):C820–30.  https://doi.org/10.1152/ajpcell.00233.2016.CrossRefPubMedPubMedCentralGoogle Scholar
  67. Katzir Z, Dinour D, Reznik-Wolf H, Nissenkorn A, Holtzman E. Familial pure proximal renal tubular acidosis-a clinical and genetic study. Nephrol Dial Transplant. 2008;23:1211–5.CrossRefPubMedGoogle Scholar
  68. Kim YH, Kwon TH, Christensen BM, Nielsen J, Wall SM, Madsen KM, et al. Altered expression of renal acid-base transporters in rats with lithium-induced NDI. Am J Phys Renal Phys. 2003;285:F1244–57.Google Scholar
  69. Kreindler JL, Peters KW, Frizzell RA, Bridges RJ. Identification and membrane localization of electrogenic sodium bicarbonate cotransporters in Calu-3 cells. Biochim Biophys Acta. 2006;1762:704–10.CrossRefPubMedGoogle Scholar
  70. Kristensen JM, Kristensen M, Juel C. Expression of Na+/HCO3 co-transporter proteins (NBCs) in rat and human skeletal muscle. Acta Physiol Scand. 2004;182:69–76.CrossRefPubMedGoogle Scholar
  71. Kunimi M, Seki G, Hara C, Taniguchi S, Uwatoko S, Goto A, et al. Dopamine inhibits renal Na+:HCO3 cotransporter in rabbits and normotensive rats but not in spontaneously hypertensive rats. Kidney Int. 2000;57:534–43.CrossRefPubMedGoogle Scholar
  72. Kurtz I. SLC4 sodium-driven bicarbonate transporters. In: Alperin RJ, Caplan M, Moe OW, editors. Seldin and Giebisch’s The Kidney: Physiology and Pathophysiology. Amsterdam/Boston: Elsevier/Academic Press; 2013. p. 1837–60.CrossRefGoogle Scholar
  73. Kurtz I, Petrasek D, Tatishchev S. Molecular mechanisms of electrogenic sodium bicarbonate cotransport: structural and equilibrium thermodynamic considerations. J Membr Biol. 2004;197:77–90.CrossRefPubMedGoogle Scholar
  74. Lacruz RS, Nanci A, White SN, Wen X, Wang H, Zalzal SF, et al. The sodium bicarbonate cotransporter (NBCe1) is essential for normal development of mouse dentition. J Biol Chem. 2010;285:24432–8.PubMedPubMedCentralCrossRefGoogle Scholar
  75. Lacruz RS, Smith CE, Moffatt P, Chang EH, Bromage TG, Bringas Jr P, et al. Requirements for ion and solute transport, and pH regulation during enamel maturation. J Cell Physiol. 2012;227:1776–85.  https://doi.org/10.1002/jcp.22911.CrossRefPubMedPubMedCentralGoogle Scholar
  76. Lee SH, Park JH, Jung HH, Lee SH, Oh JW, Lee HM, et al. Expression and distribution of ion transport mRNAs in human nasal mucosa and nasal polyps. Acta Otolaryngol. 2005;125:745–52.CrossRefPubMedGoogle Scholar
  77. Lee SK, Grichtchenko II, Boron WF. Distinguishing HCO3 from CO32− transport by NBCe1-A. FASEB J. 2011;25:656.9.Google Scholar
  78. Lee SK, Boron WF, Parker MD. Relief of autoinhibition of the electrogenic Na-HCO3 cotransporter NBCe1-B: role of IRBIT vs.amino-terminal truncation. Am J Physiol. 2012;302:C518–26.CrossRefGoogle Scholar
  79. Lee SK, Boron WF, Parker MD. Substrate specificity of the electrogenic sodium/bicarbonate cotransporter NBCe1-A (SLC4A4, variant A) from humans and rabbits. Am J Phys Renal Phys. 2013;304:F883–99.Google Scholar
  80. Lemann Jr J, Adams ND, Wilz DR, Brenes LG. Acid and mineral balances and bone in familial proximal renal tubular acidosis. Kidney Int. 2000;58:1267–77.CrossRefPubMedGoogle Scholar
  81. Lewis SE, Erickson RP, Barnett LB, Venta PJ, Tashian RE. N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2 locus: an animal model for human carbonic anhydrase II deficiency syndrome. Proc Natl Acad Sci USA. 1988;85:1962–6.PubMedPubMedCentralCrossRefGoogle Scholar
  82. Li HC, Worrell RT, Matthews JB, Husseinzadeh H, Neumeier L, Petrovic S, et al. Identification of a carboxyl-terminal motif essential for the targeting of Na+-HCO3 cotransporter NBC1 to the basolateral membrane. J Biol Chem. 2004;279:43190–7.CrossRefPubMedGoogle Scholar
  83. Li HC, Szigligeti P, Worrell RT, Matthews JB, Conforti L, Soleimani M. Missense mutations in Na+:HCO3 cotransporter NBC1 show abnormal trafficking in polarized kidney cells: a basis of proximal renal tubular acidosis. Am J Physiol Renal Physiol. 2005;289:F61–71.CrossRefPubMedGoogle Scholar
  84. Liu Y, Xu JY, Wang DK, Wang L, Chen LM. 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.  https://doi.org/10.1016/j.ygeno.2011.04.010.CrossRefPubMedGoogle Scholar
  85. Liu Y, Yang J, Chen LM. Structure and function of SLC4 family HCO3 transporters. Front Physiol. 2015;6:355.  https://doi.org/10.3389/fphys.2015.00355.CrossRefPubMedPubMedCentralGoogle Scholar
  86. Lo YF, Yang SS, 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.CrossRefPubMedGoogle Scholar
  87. Lu J, Boron WF. Reversible and irreversible interactions of DIDS with the human electrogenic Na/HCO3 cotransporter NBCe1-A: role of lysines in the KKMIK motif of TM5. Am J Physiol. 2007;292:C1787–98.CrossRefGoogle Scholar
  88. Lu J, Daly CM, Parker MD, Gill HS, Piermarini PM, Pelletier MF, et al. Effect of human carbonic anhydrase II on the activity of the human electrogenic Na/HCO3 cotransporter NBCe1-A in Xenopus oocytes. J Biol Chem. 2006;281:19241–50.CrossRefPubMedGoogle Scholar
  89. Majumdar D, Maunsbach AB, Shacka JJ, Williams JB, Berger UV, Schultz KP, et al. Localization of electrogenic Na/bicarbonate cotransporter NBCe1 variants in rat brain. Neuroscience. 2008;155:818–32.  https://doi.org/10.1016/j.neuroscience.2008.05.037.CrossRefPubMedGoogle Scholar
  90. Marino CR, Jeanes V, Boron WF, Schmitt BM. Expression and distribution of the Na+-HCO3 cotransporter in human pancreas. Am J Physiol. 1999;277:G487–94.PubMedGoogle Scholar
  91. Maunsbach AB, Vorum H, Kwon TH, Nielsen S, Simonsen B, Choi I, et al. Immunoelectron microscopic localization of the electrogenic Na/HCO3 cotransporter in rat and ambystoma kidney. J Am Soc Nephrol. 2000;11:2179–89.PubMedGoogle Scholar
  92. McAlear SD, Bevensee MO. A cysteine-scanning mutagenesis study of transmembrane domain 8 of the electrogenic sodium/bicarbonate cotransporter NBCe1. J Biol Chem. 2006;281:32417–27.CrossRefPubMedGoogle Scholar
  93. McAlear SD, Liu X, Williams JB, McNicholas-Bevensee CM, Bevensee MO. Electrogenic Na/HCO3 cotransporter (NBCe1) variants expressed in Xenopus oocytes: functional comparison and roles of the amino and carboxy termini. J General Physiol. 2006;127:639–58.  https://doi.org/10.1085/jgp.200609520.CrossRefGoogle Scholar
  94. Mohebbi N, Kovacikova J, Nowik M, Wagner CA. Thyroid hormone deficiency alters expression of acid-base transporters in rat kidney. Am J Phys Renal Phys. 2007;293:F416–27.Google Scholar
  95. Mohebbi N, Mihailova M, Wagner CA. The calcineurin inhibitor FK506 (tacrolimus) is associated with transient metabolic acidosis and altered expression of renal acid-base transport proteins. Am J Phys Renal Phys. 2009;297:F499–509.Google Scholar
  96. Moser AJ, Gangopadhyay A, Bradbury NA, Peters KW, Frizzell RA, Bridges RJ. Electrogenic bicarbonate secretion by prairie dog gallbladder. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1683–94.CrossRefPubMedGoogle Scholar
  97. Müller-Berger S, Nesterov VV, Frömter E. Partial recovery of in vivo function by improved incubation conditions of isolated renal proximal tubule. II. Change of Na-HCO3 cotransport stoichiometry and of response to acetazolamide. Pflugers Arch. 1997;434:383–91.CrossRefPubMedGoogle Scholar
  98. Muller-Berger S, Ducoudret O, Diakov A, Fromter E. The renal Na-HCO3 cotransporter expressed in Xenopus laevis oocytes: change in stoichiometry in response to elevation of cytosolic Ca2+ concentration. Pflugers Arch - Eur J Physiol. 2001;442:718–28.CrossRefGoogle Scholar
  99. Myers EJ, Yuan L, Felmlee MA, Lin YY, Jiang Y, Pei Y, et al. A novel mutant Na+/HCO3 cotransporter NBCe1 in a case of compound-heterozygous inheritance of proximal renal tubular acidosis. J Physiol. 2016.  https://doi.org/10.1113/JP272252.CrossRefPubMedPubMedCentralGoogle Scholar
  100. Namkoong E, Shin YH, Bae JS, Choi S, Kim M, Kim N, et al. Role of sodium bicarbonate cotransporters in intracellular ph regulation and their regulatory mechanisms in human submandibular glands. PLoS One. 2015;10:e0138368.  https://doi.org/10.1371/journal.pone.0138368.CrossRefPubMedPubMedCentralGoogle Scholar
  101. Nudelman I, Rebibo-Sabbah A, Cherniavsky M, Belakhov V, Hainrichson M, Chen F, et al. Development of novel aminoglycoside (NB54) with reduced toxicity and enhanced suppression of disease-causing premature stop mutations. J Med Chem. 2009;52:2836–45.PubMedPubMedCentralCrossRefGoogle Scholar
  102. Orlowski A, De Giusti VC, Morgan PE, Aiello EA, Alvarez BV. Binding of carbonic anhydrase IX to extracellular loop 4 of the NBCe1 Na+/HCO3 cotransporter enhances NBCe1-mediated HCO3 influx in the rat heart. Am J Physiol Cell Physiol. 2012;303:C69–80.  https://doi.org/10.1152/ajpcell.00431.2011.CrossRefPubMedGoogle Scholar
  103. Paine ML, Snead ML, Wang HJ, Abuladze N, Pushkin A, Liu W, et al. Role of NBCe1 and AE2 in secretory ameloblasts. J Dent Res. 2008;87:391–5.PubMedCrossRefGoogle Scholar
  104. Park HW, Lee MG. Transepithelial bicarbonate secretion: Lessons from the pancreas. Cold Spring Harb Perspect Med. 2012;2(10):a009571.  https://doi.org/10.1101/cshperspect.a009571.CrossRefPubMedPubMedCentralGoogle Scholar
  105. Parker MD, Boron WF. The divergence, actions, roles, and relatives of sodium-coupled bicarbonate transporters. Physiol Rev. 2013;93:803–959.PubMedPubMedCentralCrossRefGoogle Scholar
  106. Parker MD, Qin X, Williamson RC, Toye AM, Boron WF. HCO3-independent conductance with a mutant Na+/HCO3 cotransporter (SLC4A4) in a case of proximal renal tubular acidosis with hypokalaemic paralysis. J Physiol. 2012;590:2009–34.PubMedPubMedCentralCrossRefGoogle Scholar
  107. Peltz SW, Morsy M, Welch EM, Jacobson A. Ataluren as an agent for therapeutic nonsense suppression. Annu Rev Med. 2013;64:407–25.CrossRefPubMedGoogle Scholar
  108. Pena-Munzenmayer G, George AT, Shull GE, Melvin JE, Catalan MA. Ae4 (Slc4a9) is an electroneutral monovalent cation-dependent Cl-/HCO3 exchanger. J General Physiol. 2016;147:423–36.  https://doi.org/10.1085/jgp.201611571.PubMedPubMedCentralCrossRefGoogle Scholar
  109. Perry C, Blaine J, Le H, Grichtchenko II. PMA- and ANG II-induced PKC regulation of the renal Na+-HCO3 cotransporter (hkNBCe1). Am J Physiol Ren Physiol. 2006;290:F417–27.CrossRefGoogle Scholar
  110. Perry C, Le H, Grichtchenko II. ANG II and calmodulin/CaMKII regulate surface expression and functional activity of NBCe1 via separate means. Am J Phys Renal Phys. 2007;293:F68–77.Google Scholar
  111. Perry C, Baker OJ, Reyland ME, Grichtchenko II. PKCαβγ- and PKCδ-dependent endocytosis of NBCe1-A and NBCe1-B in salivary parotid acinar cells. Am J Physiol. 2009;297:C1409–23.CrossRefGoogle Scholar
  112. Piermarini PM, Kim EY, Boron WF. Evidence against a direct interaction between intracellular carbonic anhydrase II and pure C-terminal domains of SLC4 bicarbonate transporters. J Biol Chem. 2007;282:1409–21.CrossRefPubMedGoogle Scholar
  113. Planelles G, Thomas SR, Anagnostopoulos T. Change of apparent stoichiometry of proximal-tubule Na+-HCO3 cotransport upon experimental reversal of its orientation. Proc Natl Acad Sci USA. 1993;90:7406–10.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 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.  https://doi.org/10.1113/jphysiol.2004.065110.CrossRefPubMedPubMedCentralGoogle Scholar
  115. Rebello G, Ramesar R, Vorster A, Roberts L, Ehrenreich L, Oppon E, et al. Apoptosis-inducing signal sequence mutation in carbonic anhydrase IV identified in patients with the RP17 form of retinitis pigmentosa. Proc Natl Acad Sci USA. 2004;101:6617–22.PubMedPubMedCentralCrossRefGoogle Scholar
  116. Rector Jr FC, Bloomer HA, Seldin DW. Effect of potassium deficiency on the reabsorption of bicarbonate in the proximal tubule of the rat kidney. J Clin Investig. 1964;43:1976–82.PubMedPubMedCentralCrossRefGoogle Scholar
  117. Reithmeier RA, Casey JR, Kalli AC, Sansom MS, Alguel Y, Iwata S. Band 3, the human red cell chloride/bicarbonate anion exchanger (AE1, SLC4A1), in a structural context. Biochim Biophys Acta. 2016;1858:1507–32.  https://doi.org/10.1016/j.bbamem.2016.03.030.CrossRefPubMedGoogle Scholar
  118. Roberts KE, Randall HT, Sanders HL, Hood M. Effects of potassium on renal tubular reabsorption of bicarbonate. J Clin Investig. 1955;34:666–72.PubMedPubMedCentralCrossRefGoogle Scholar
  119. Romero MF, Hediger MA, Boulpaep EL, Boron WF. Expression cloning and characterization of a renal electrogenic Na+/HCO3 cotransporter. Nature. 1997;387:409–13.  https://doi.org/10.1038/387409a0.CrossRefPubMedGoogle Scholar
  120. Sasaki S, Marumo F. Mechanisms of inhibition of proximal acidification by PTH. Am J Physiol. 1991;260:F833–8.PubMedGoogle Scholar
  121. Satoh H, Moriyama N, Hara C, Yamada H, Horita S, Kunimi M, et al. Localization of Na+-HCO3 cotransporter (NBC-1) variants in rat and human pancreas. Am J Physiol. 2003;284:C729–37.CrossRefGoogle Scholar
  122. Schueler C, Becker HM, McKenna R, Deitmer JW. Transport activity of the sodium bicarbonate cotransporter NBCe1 is enhanced by different isoforms of carbonic anhydrase. PLoS One. 2011;6:e27167.PubMedPubMedCentralCrossRefGoogle Scholar
  123. Seki G, Coppola S, Frömter E. The Na+-HCO3 cotransporter operates with a coupling ratio of 2 HCO3 to 1 Na+ in isolated rabbit renal proximal tubule. Pflugers Arch. 1993;425:409–16.CrossRefPubMedGoogle Scholar
  124. Seki G, Yamada H, Horita S, Suzuki M, Sekine T, Igarashi T, et al. Activation and inactivation mechanisms of Na-HCO3 cotransporter NBC1. J Epithelial Biol Pharmacol. 2008;1:35–9.  https://doi.org/10.2174/1875044300801010035.CrossRefGoogle Scholar
  125. Sergeev M, Godin AG, Kao L, Abuladze N, Wiseman PW, Kurtz I. Determination of membrane protein transporter oligomerization in native tissue using spatial fluorescence intensity fluctuation analysis. PLoS One. 2012;7:e36215.PubMedPubMedCentralCrossRefGoogle Scholar
  126. Shcheynikov N, Son A, Hong JH, Yamazaki O, Ohana E, Kurtz I, et al. Intracellular Cl- as a signaling ion that potently regulates Na+/HCO3 transporters. Proc Natl Acad Sci USA. 2015;112:E329–37.  https://doi.org/10.1073/pnas.1415673112.
  127. 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 USA. 2006;103:9542–9547.CrossRefGoogle Scholar
  128. Shnitsar V, Li J, Li X, Calmettes C, Basu A, Casey JR, et al. A substrate access tunnel in the cytosolic domain is not an essential feature of the solute carrier 4 (SLC4) family of bicarbonate transporters. J Biol Chem. 2013;288:33848–60.  https://doi.org/10.1074/jbc.M113.511865.CrossRefPubMedPubMedCentralGoogle Scholar
  129. Skelton LA, Boron WF, Zhou Y. Acid-base transport by the renal proximal tubule. J Nephrol. 2010;23(Suppl 16):S4–18.PubMedPubMedCentralGoogle Scholar
  130. Sly WS, Whyte MP, Sundaram V, Tashian RE, Hewett-Emmett D, Guibaud P, et al. Carbonic anhydrase II deficiency in 12 families with the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. N Engl J Med. 1985;313:139–45.PubMedCrossRefGoogle Scholar
  131. Sonalker PA, Tofovic SP, Jackson EK. Increased expression of the sodium transporter BSC-1 in spontaneously hypertensive rats. J Pharmacol Exp Ther. 2004;311:1052–61.CrossRefPubMedGoogle Scholar
  132. Sonalker PA, Tofovic SP, Bastacky SI, Jackson EK. Chronic noradrenaline increases renal expression of NHE-3, NBC-1, BSC-1 and aquaporin-2. Clin Exp Pharmacol Physiol. 2008;35:594–600.CrossRefPubMedGoogle Scholar
  133. Spackman T, Fuchs F, Assali NS. Acid-base status of the fetus in human pregnancy. Obstet Gynecol. 1963;22:785–91.PubMedGoogle Scholar
  134. Suzuki M, Vaisbich MH, Yamada H, Horita S, Li Y, Sekine T, et al. Functional analysis of a novel missense NBC1 mutation and of other mutations causing proximal renal tubular acidosis. Pflugers Arch. 2008;455:583–93.CrossRefPubMedGoogle Scholar
  135. Suzuki M, Van Paesschen W, Stalmans I, Horita S, Yamada H, Bergmans BA, et al. Defective membrane expression of the Na+-HCO3 cotransporter NBCe1 is associated with familial migraine. Proc Natl Acad Sci USA. 2010;107:15963–8.PubMedPubMedCentralCrossRefGoogle Scholar
  136. Tang XB, Kovacs M, Sterling D, Casey JR. Identification of residues lining the translocation pore of human AE1, plasma membrane anion exchange protein. J Biol Chem. 1999;274:3557–64.CrossRefPubMedGoogle Scholar
  137. Thornell IM, Bevensee MO. Phosphatidylinositol 4,5-bisphosphate degradation inhibits the Na+/bicarbonate cotransporter NBCe1-B and -C variants expressed in Xenopus oocytes. J Physiol. 2015;593:541–58.  https://doi.org/10.1113/jphysiol.2014.284307.CrossRefPubMedPubMedCentralGoogle Scholar
  138. Thornell IM, Wu J, Liu X, Bevensee MO. PIP2 hydrolysis stimulates the electrogenic Na+−bicarbonate cotransporter NBCe1-B and -C variants expressed in Xenopus laevis oocytes. J Physiol. 2012;590:5993–6011.  https://doi.org/10.1113/jphysiol.2012.242479.CrossRefPubMedPubMedCentralGoogle Scholar
  139. Toye AM, Parker MD, Daly CM, Lu J, Virkki LV, Pelletier MF, et al. The human NBCe1-A mutant R881C, associated with proximal renal tubular acidosis, retains function but is mistargeted in polarized renal epithelia. Am J Physiol. 2006;291:C788–801.CrossRefGoogle Scholar
  140. Usui T, Hara M, Satoh H, Moriyama N, Kagaya H, Amano S, et al. Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis. J Clin Invest. 2001;108:107–15.PubMedPubMedCentralCrossRefGoogle Scholar
  141. Velic A, Hirsch JR, Bartel J, Thomas R, Schroter R, Stegemann H, et al. Renal transplantation modulates expression and function of receptors and transporters of rat proximal tubules. J Am Soc Nephrol. 2004;15:967–77.CrossRefPubMedGoogle Scholar
  142. Vilas GL, Loganathan SK, Liu J, Riau AK, Young JD, Mehta JS, et al. Transmembrane water-flux through SLC4A11: a route defective in genetic corneal diseases. Hum Mol Genet. 2013;22:4579–90.  https://doi.org/10.1093/hmg/ddt307.CrossRefPubMedPubMedCentralGoogle Scholar
  143. Wang G, Li C, Kim SW, Ring T, Wen J, Djurhuus JC, et al. Ureter obstruction alters expression of renal acid-base transport proteins in rat kidney. Am J Phys Renal Phys. 2008;295:F497–506.Google Scholar
  144. Watanabe A, Choe S, Chaptal V, Rosenberg JM, Wright EM, Grabe M, et al. The mechanism of sodium and substrate release from the binding pocket of vSGLT. Nature. 2010;468:988–91.PubMedPubMedCentralCrossRefGoogle Scholar
  145. Wen X, Kurtz I, Paine ML. 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.  https://doi.org/10.1371/journal.pone.0097318.CrossRefPubMedPubMedCentralGoogle Scholar
  146. Wolosin JM, Alvarez LJ, Candia OA. HCO3 transport in the toad lens epithelium is mediated by an electronegative Na+-dependent symport. Am J Physiol. 1990;258:C855–61.CrossRefPubMedGoogle Scholar
  147. Wolosin JM, Chen M, Gordon RE, Stegman Z, Butler GA. Separation of the rabbit ciliary body epithelial layers in viable form: identification of differences in bicarbonate transport. Exp Eye Res. 1993;56:401–9.PubMedCrossRefGoogle Scholar
  148. Wu J, McNicholas CM, Bevensee MO. Phosphatidylinositol 4,5-bisphosphate (PIP2) stimulates the electrogenic Na/HCO3 cotransporter NBCe1-A expressed in Xenopus oocytes. Proc Natl Acad Sci USA. 2009;106:14150–5.  https://doi.org/10.1073/pnas.0906303106.CrossRefGoogle Scholar
  149. Yamada H, Horita S, Suzuki M, Fujita T, Seki G. Functional role of a putative carbonic anhydrase II-binding domain in the electrogenic Na+-HCO3 cotransporter NBCe1 expressed in Xenopus oocytes. Channels (Austin). 2011;5:106–9.CrossRefGoogle Scholar
  150. Yamaguchi S, Ishikawa T. Electrophysiological characterization of native Na+-HCO3 cotransporter current in bovine parotid acinar cells. J Physiol. 2005;568:181–97.PubMedPubMedCentralCrossRefGoogle Scholar
  151. Yamaguchi S, Ishikawa T. The electrogenic Na+-HCO3 cotransporter NBCe1-B is regulated by intracellular Mg2+. Biochem Biophys Res Commun. 2008;376:100–4.PubMedCrossRefGoogle Scholar
  152. Yamaguchi S, Ishikawa T. IRBIT reduces the apparent affinity for intracellular Mg2+ in inhibition of the electrogenic Na+-HCO3 cotransporter NBCe1-B. Biochem Biophys Res Commun. 2012;424:433–8.PubMedCrossRefGoogle Scholar
  153. Yamashita A, Singh SK, Kawate T, Jin Y, Gouaux E. Crystal structure of a bacterial homologue of Na+/Cl-dependent neurotransmitter transporters. Nature. 2005;437:215–23.PubMedCrossRefGoogle Scholar
  154. Yamazaki O, Yamada H, Suzuki M, Horita S, Shirai A, Nakamura M, et al. Functional characterization of nonsynonymous single nucleotide polymorphisms in the electrogenic Na+-HCO3 cotransporter NBCe1A. Pflugers Arch. 2011;461:249–59.PubMedCrossRefGoogle Scholar
  155. Yamazaki O, Yamada H, Suzuki M, Horita S, Shirai A, Nakamura M, et al. Identification of dominant negative effect of L522P mutation in the electrogenic Na+-HCO3 cotransporter NBCe1. Pflugers Arch. 2013;465:1281–91.CrossRefPubMedGoogle Scholar
  156. Yang HS, Kim E, Lee S, Park HJ, Cooper DS, Rajbhandari I, et al. Mutation of aspartate 555 of the sodium/bicarbonate transporter SLC4A4/NBCe1 induces chloride transport. J Biol Chem. 2009;284:15970–9.PubMedPubMedCentralCrossRefGoogle Scholar
  157. Yang D, Li Q, So I, Huang CL, Ando H, Mizutani A, et al. IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK kinase pathway. J Clin Investig. 2011;121:956–65.PubMedPubMedCentralCrossRefGoogle Scholar
  158. Yoshitomi K, Burckhardt BC, Frömter E. Rheogenic sodium-bicarbonate cotransport in the peritubular cell membrane of rat renal proximal tubule. Pflugers Arch. 1985;405:360–6.PubMedCrossRefGoogle Scholar
  159. Yu H, Riederer B, Stieger N, Boron WF, Shull GE, Manns MP, et al. Secretagogue stimulation enhances NBCe1 (electrogenic Na+/HCO3 cotransporter) surface expression in murine colonic crypts. Am J Physiol Gastrointest Liver Physiol. 2009;297:G1223–31.PubMedPubMedCentralCrossRefGoogle Scholar
  160. Yu Q, Liu X, Liu Y, Riederer B, Li T, Tian DA, et al. Defective small intestinal anion secretion, dipeptide absorption, and intestinal failure in suckling NBCe1-deficient mice. Pflugers Arch – Eur J Physiol. 2016;468:1419–32.  https://doi.org/10.1007/s00424-016-1836-3.CrossRefGoogle Scholar
  161. Zhang W, Ogando DG, Bonanno JA, Obukhov AG. Human SLC4A11 is a novel NH3/H+ Co-transporter. J Biol Chem. 2015;290:16894–905.  https://doi.org/10.1074/jbc.M114.627455.CrossRefPubMedPubMedCentralGoogle Scholar
  162. Zheng Y, Horita S, Hara C, Kunimi M, Yamada H, Sugaya T, et al. Biphasic regulation of renal proximal bicarbonate absorption by luminal AT1A receptor. J Am Soc Nephrol. 2003;14:1116–22.CrossRefPubMedGoogle Scholar
  163. Zhu Q, Casey JR. The substrate anion selectivity filter in the human erythrocyte Cl/HCO3 exchange protein, AE1. J Biol Chem. 2004;279:23565–73.CrossRefPubMedGoogle Scholar
  164. Zhu Q, Lee DW, Casey JR. Novel topology in C-terminal region of the human plasma membrane anion exchanger, AE1. J Biol Chem. 2003;278:3112–20.PubMedCrossRefGoogle Scholar
  165. Zhu Q, Azimov R, Kao L, Newman D, Liu W, Abuladze N, et al. NBCe1-A transmembrane segment 1 lines the ion translocation pathway. J Biol Chem. 2009;284:8918–29.  https://doi.org/10.1074/jbc.M806674200.CrossRefPubMedPubMedCentralGoogle Scholar
  166. Zhu Q, Kao L, Azimov R, Abuladze N, Newman D, Pushkin A, et al. Structural and functional characterization of the C-terminal transmembrane region of NBCe1-A. J Biol Chem. 2010a;285:37178–87.PubMedPubMedCentralCrossRefGoogle Scholar
  167. Zhu Q, Kao L, Azimov R, Newman D, Liu W, Pushkin A, et al. Topological location and structural importance of the NBCe1-A residues mutated in proximal renal tubular acidosis. J Biol Chem. 2010b;285:13416–26.  https://doi.org/10.1074/jbc.M109.093286.CrossRefPubMedPubMedCentralGoogle Scholar
  168. Zhu Q, Liu W, Kao L, Azimov R, Newman D, Abuladze N, et al. Topology of NBCe1 protein transmembrane segment 1 and structural effect of proximal renal tubular acidosis (pRTA) S427L mutation. J Biol Chem. 2013a;288:7894–906.PubMedPubMedCentralCrossRefGoogle Scholar
  169. Zhu Q, Shao XM, Kao L, Azimov R, Weinstein AM, Newman D, et al. Missense mutation T485S alters NBCe1-A electrogenicity causing proximal renal tubular acidosis. Am J Physiol. 2013b;305:C392–405.CrossRefGoogle Scholar
  170. Zhu Q, Kao L, Azimov R, Abuladze N, Newman D, Kurtz I. Interplay between disulfide bonding and N-glycosylation defines SLC4 Na+coupled transporter extracellular topography. J Biol Chem. 2015;290:5391–404.  https://doi.org/10.1074/jbc.M114.619320.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Division of NephrologyDavid Geffen School of Medicine, and Brain Research InstituteLos AngelesUSA