Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Am J Physiol Cell Physiol
2009 Oct 01;2974:C865-75. doi: 10.1152/ajpcell.00679.2008.
Show Gene links
Show Anatomy links
Cloning, localization, and functional expression of the electrogenic Na+ bicarbonate cotransporter (NBCe1) from zebrafish.
Sussman CR
,
Zhao J
,
Plata C
,
Lu J
,
Daly C
,
Angle N
,
DiPiero J
,
Drummond IA
,
Liang JO
,
Boron WF
,
Romero MF
,
Chang MH
.
???displayArticle.abstract???
Mutations in the electrogenic Na+/nHCO3- cotransporter (NBCe1, SLC4A4) cause severe proximal renal tubular acidosis, glaucoma, and cataracts in humans, indicating NBCe1 has a critical role in acid-base homeostasis and ocular fluid transport. To better understand the homeostatic roles and protein ontogeny of NBCe1, we have cloned, localized, and downregulated NBCe1 expression in zebrafish, and examined its transport characteristics when expressed in Xenopus oocytes. Zebrafish NBCe1 (zNBCe1) is 80% identical to published mammalian NBCe1 cDNAs. Like other fish NBCe1 clones, zebrafish NBCe1 is most similar to the pancreatic form of mammalian NBC (Slc4a4-B) but appears to be the dominant isoform found in zebrafish. In situ hybridization of embryos demonstrated mRNA expression in kidney pronephros and eye by 24 h postfertilization (hpf) and gill and brain by 120 hpf. Immunohistochemical labeling demonstrated expression in adult zebrafish eye and gill. Morpholino knockdown studies demonstrated roles in eye and brain development and caused edema, indicating altered fluid and electrolyte balance. With the use of microelectrodes to measure membrane potential (Vm), voltage clamp (VC), intracellular pH (pH(i)), or intracellular Na+ activity (aNa(i)), we examined the function of zNBCe1 expressed in Xenopus oocytes. Zebrafish NBCe1 shared transport properties with mammalian NBCe1s, demonstrating electrogenic Na+ and HCO3- transport as well as similar drug sensitivity, including inhibition by 4,4'-diiso-thiocyano-2,2'-disulfonic acid stilbene and tenidap. These data indicate that NBCe1 in zebrafish shares many characteristics with mammalian NBCe1, including tissue distribution, importance in systemic water and electrolyte balance, and electrogenic transport of Na+ and HCO3-. Thus zebrafish promise to be useful model system for studies of NBCe1 physiology.
Abuladze,
Structural organization of the human NBC1 gene: kNBC1 is transcribed from an alternative promoter in intron 3.
2000, Pubmed
Abuladze,
Structural organization of the human NBC1 gene: kNBC1 is transcribed from an alternative promoter in intron 3.
2000,
Pubmed
Bachmann,
cAMP-mediated regulation of murine intestinal/pancreatic Na+/HCO3- cotransporter subtype pNBC1.
2003,
Pubmed
Bevensee,
An electrogenic Na(+)-HCO(-)(3) cotransporter (NBC) with a novel COOH-terminus, cloned from rat brain.
2000,
Pubmed
,
Xenbase
Bok,
Immunolocalization of electrogenic sodium-bicarbonate cotransporters pNBC1 and kNBC1 in the rat eye.
2001,
Pubmed
Boron,
Intracellular pH regulation in the renal proximal tubule of the salamander. Basolateral HCO3- transport.
1983,
Pubmed
Bulat,
Transventricular and transpial absorption of cerebrospinal fluid into cerebral microvessels.
2008,
Pubmed
Chang,
Entry to "formula tunnel" revealed by SLC4A4 human mutation and structural model.
2008,
Pubmed
,
Xenbase
Choi,
Cloning and characterization of a human electrogenic Na+-HCO-3 cotransporter isoform (hhNBC).
1999,
Pubmed
,
Xenbase
Claiborne,
Acid-base regulation in fishes: cellular and molecular mechanisms.
2002,
Pubmed
Deigweiher,
Acclimation of ion regulatory capacities in gills of marine fish under environmental hypercapnia.
2008,
Pubmed
Demirci,
Proximal renal tubular acidosis and ocular pathology: a novel missense mutation in the gene (SLC4A4) for sodium bicarbonate cotransporter protein (NBCe1).
2006,
Pubmed
,
Xenbase
Dinour,
A novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through ion transport defects.
2004,
Pubmed
,
Xenbase
Drummond,
Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function.
1998,
Pubmed
Drummond,
Kidney development and disease in the zebrafish.
2005,
Pubmed
Ducoudret,
The renal Na-HCO3-cotransporter expressed in Xenopus laevis oocytes: inhibition by tenidap and benzamil and effect of temperature on transport rate and stoichiometry.
2001,
Pubmed
,
Xenbase
García-Lecea,
In vivo analysis of choroid plexus morphogenesis in zebrafish.
2008,
Pubmed
Gawenis,
Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter.
2007,
Pubmed
Giffard,
The electrogenic sodium bicarbonate cotransporter: developmental expression in rat brain and possible role in acid vulnerability.
2000,
Pubmed
,
Xenbase
Goessling,
Ultrasound biomicroscopy permits in vivo characterization of zebrafish liver tumors.
2007,
Pubmed
Goss,
Evidence for a morphological component in acid-base regulation during environmental hypercapnia in the brown bullhead (Ictalurus nebulosus).
1992,
Pubmed
Hirata,
Mechanism of acid adaptation of a fish living in a pH 3.5 lake.
2003,
Pubmed
,
Xenbase
Igarashi,
Unraveling the molecular pathogenesis of isolated proximal renal tubular acidosis.
2002,
Pubmed
Igarashi,
Novel nonsense mutation in the Na+/HCO3- cotransporter gene (SLC4A4) in a patient with permanent isolated proximal renal tubular acidosis and bilateral glaucoma.
2001,
Pubmed
Jacobs,
Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability.
2008,
Pubmed
Jensen,
Localization of sodium bicarbonate cotransporter (NBC) protein and messenger ribonucleic acid in rat epididymis.
1999,
Pubmed
Kurita,
Identification of intestinal bicarbonate transporters involved in formation of carbonate precipitates to stimulate water absorption in marine teleost fish.
2008,
Pubmed
,
Xenbase
Lowery,
Initial formation of zebrafish brain ventricles occurs independently of circulation and requires the nagie oko and snakehead/atp1a1a.1 gene products.
2005,
Pubmed
Lu,
Reversible and irreversible interactions of DIDS with the human electrogenic Na/HCO3 cotransporter NBCe1-A: role of lysines in the KKMIK motif of TM5.
2007,
Pubmed
,
Xenbase
McAlear,
Electrogenic Na/HCO3 cotransporter (NBCe1) variants expressed in Xenopus oocytes: functional comparison and roles of the amino and carboxy termini.
2006,
Pubmed
,
Xenbase
Nichane,
The Na+/PO4 cotransporter SLC20A1 gene labels distinct restricted subdomains of the developing pronephros in Xenopus and zebrafish embryos.
2006,
Pubmed
,
Xenbase
Parks,
Interactions between Na+ channels and Na+-HCO3- cotransporters in the freshwater fish gill MR cell: a model for transepithelial Na+ uptake.
2007,
Pubmed
Perry,
Integrated responses of Na+/HCO3- cotransporters and V-type H+-ATPases in the fish gill and kidney during respiratory acidosis.
2003,
Pubmed
Praetorius,
Molecular and functional evidence for electrogenic and electroneutral Na(+)-HCO(3)(-) cotransporters in murine duodenum.
2001,
Pubmed
Rickmann,
Distinct expression and subcellular localization patterns of Na+/HCO3- cotransporter (SLC 4A4) variants NBCe1-A and NBCe1-B in mouse brain.
2007,
Pubmed
Romero,
The electrogenic Na+/HCO3- cotransporter, NBC.
2001,
Pubmed
,
Xenbase
Romero,
Cloning and characterization of a Na+-driven anion exchanger (NDAE1). A new bicarbonate transporter.
2000,
Pubmed
,
Xenbase
Romero,
Physiology of electrogenic SLC26 paralogues.
2006,
Pubmed
,
Xenbase
Romero,
Expression cloning and characterization of a renal electrogenic Na+/HCO3- cotransporter.
1997,
Pubmed
,
Xenbase
Romero,
Cloning and functional expression of rNBC, an electrogenic Na(+)-HCO3- cotransporter from rat kidney.
1998,
Pubmed
,
Xenbase
Roos,
Intracellular pH.
1981,
Pubmed
Rossmann,
Na+/HCO3- cotransport and expression of NBC1 and NBC2 in rabbit gastric parietal and mucous cells.
1999,
Pubmed
Roussa,
Immunolocalization of anion exchanger AE2 and Na(+)-HCO(-)(3) cotransporter in rat parotid and submandibular glands.
1999,
Pubmed
Schmitt,
Immunolocalization of the electrogenic Na+-HCO-3 cotransporter in mammalian and amphibian kidney.
1999,
Pubmed
,
Xenbase
Sciortino,
Cation and voltage dependence of rat kidney electrogenic Na(+)-HCO(-)(3) cotransporter, rkNBC, expressed in oocytes.
1999,
Pubmed
,
Xenbase
Sciortino,
Localization of endogenous and recombinant Na(+)-driven anion exchanger protein NDAE1 from Drosophila melanogaster.
2001,
Pubmed
,
Xenbase
Shirakabe,
IRBIT, an inositol 1,4,5-trisphosphate receptor-binding protein, specifically binds to and activates pancreas-type Na+/HCO3- cotransporter 1 (pNBC1).
2006,
Pubmed
,
Xenbase
Wingert,
The cdx genes and retinoic acid control the positioning and segmentation of the zebrafish pronephros.
2007,
Pubmed
,
Xenbase
Xie,
Molecular characterization of the murine Slc26a6 anion exchanger: functional comparison with Slc26a1.
2002,
Pubmed
,
Xenbase
