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.
???displayArticle.abstract???
HCO₃⁻ translocation across the plasma membrane via the electrogenic Na/HCO₃⁻ cotransporter NBCe1 plays an important role in intracellular pH regulation and transepithelial HCO₃⁻ transport. However, the structural determinants of transporter function remain largely unknown. A previous study showed that the putative fourth extracellular loop (EL4) plays an essential role in determining the electrogenicity of NBCe1. In the present study, we generated eight new chimeras of human NBCe1-A and NBCn1-A. All possess the putative NBCe1 EL4 and are electrogenic. Chimera O, in which the putative sixth transmembrane segment (TM6) and EL5 through the C terminus (Ct) of NBCe1 was replaced by corresponding NBCn1 sequence, produces the smallest hyperpolarization (1-2 mV) when CO₂/HCO₃⁻ is added to the extracellular solution. Biotinylation experiments show that O has a very low abundance at the plasma membrane. However, chimeras in which we simultaneously replaced the putative TM6 and smaller subdomains of the EL5-Ct region for the NBCn1 sequence were strongly electrogenic except for chimera T, in which we replaced TM6 and TM12 of NBCe1 with the corresponding regions of NBCn1. T exhibited greatly reduced transporter surface expression compared to wild-type NBCe1-A, while retaining at least some electrogenic character. We hypothesize that putative TM6 and TM12 are part of a functional unit and that if the two TMs are replaced by those of the same transporter type, high surface expression would require that the surrounding TMs are also from the same transporter type.
Abramson,
Structure and function of Na(+)-symporters with inverted repeats.
2009, Pubmed
Abramson,
Structure and function of Na(+)-symporters with inverted repeats.
2009,
Pubmed
Ahmed,
Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2.
2009,
Pubmed
Antoniou,
Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction.
2010,
Pubmed
Boedtkjer,
Disruption of Na+,HCO₃⁻ cotransporter NBCn1 (slc4a7) inhibits NO-mediated vasorelaxation, smooth muscle Ca²⁺ sensitivity, and hypertension development in mice.
2011,
Pubmed
Bok,
Blindness and auditory impairment caused by loss of the sodium bicarbonate cotransporter NBC3.
2003,
Pubmed
Bonifacino,
Signals for sorting of transmembrane proteins to endosomes and lysosomes.
2003,
Pubmed
Boron,
Modular structure of sodium-coupled bicarbonate transporters.
2009,
Pubmed
Bouyer,
Colony-stimulating factor-1 increases osteoclast intracellular pH and promotes survival via the electroneutral Na/HCO3 cotransporter NBCn1.
2007,
Pubmed
Chen,
Role of an extracellular loop in determining the stoichiometry of Na+-HCO₃⁻ cotransporters.
2011,
Pubmed
,
Xenbase
Choi,
The electrogenicity of the rat sodium-bicarbonate cotransporter NBCe1 requires interactions among transmembrane segments of the transporter.
2007,
Pubmed
,
Xenbase
Choi,
An electroneutral sodium/bicarbonate cotransporter NBCn1 and associated sodium channel.
2000,
Pubmed
,
Xenbase
De Giusti,
Angiotensin II inhibits the electrogenic Na+/HCO3- cotransport of cat cardiac myocytes.
2010,
Pubmed
De Giusti,
Role of reactive oxygen species (ROS) in angiotensin II-induced stimulation of the cardiac Na+/HCO3- cotransport.
2009,
Pubmed
Ehret,
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
2011,
Pubmed
Farhan,
Concentrative export from the endoplasmic reticulum of the gamma-aminobutyric acid transporter 1 requires binding to SEC24D.
2007,
Pubmed
Fernández-Sánchez,
Mechanisms of endoplasmic-reticulum export of glycine transporter-1 (GLYT1).
2008,
Pubmed
Grichtchenko,
Cloning, characterization, and chromosomal mapping of a human electroneutral Na(+)-driven Cl-HCO3 exchanger.
2001,
Pubmed
,
Xenbase
Horita,
Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities.
2005,
Pubmed
,
Xenbase
Ishiguro,
Variation in a bicarbonate co-transporter gene family member SLC4A7 is associated with propensity to addictions: a study using fine-mapping and three samples.
2007,
Pubmed
Khandoudi,
Inhibition of the cardiac electrogenic sodium bicarbonate cotransporter reduces ischemic injury.
2001,
Pubmed
Kumar,
SLC4A7 sodium bicarbonate co-transporter controls mitochondrial apoptosis in ischaemic coronary endothelial cells.
2011,
Pubmed
Lacruz,
The sodium bicarbonate cotransporter (NBCe1) is essential for normal development of mouse dentition.
2010,
Pubmed
Lauritzen,
NBCn1 and NHE1 expression and activity in DeltaNErbB2 receptor-expressing MCF-7 breast cancer cells: contributions to pHi regulation and chemotherapy resistance.
2010,
Pubmed
Liu,
Cloning and identification of two novel NBCe1 splice variants from mouse reproductive tract tissues: a comparative study of NCBT genes.
2011,
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
Lu,
Structure and mechanism of the uracil transporter UraA.
2011,
Pubmed
Mancias,
Structural basis of cargo membrane protein discrimination by the human COPII coat machinery.
2008,
Pubmed
Parker,
Characterization of human SLC4A10 as an electroneutral Na/HCO3 cotransporter (NBCn2) with Cl- self-exchange activity.
2008,
Pubmed
,
Xenbase
Pushkin,
Cloning, tissue distribution, genomic organization, and functional characterization of NBC3, a new member of the sodium bicarbonate cotransporter family.
1999,
Pubmed
,
Xenbase
Riihonen,
Degradation of hydroxyapatite in vivo and in vitro requires osteoclastic sodium-bicarbonate co-transporter NBCn1.
2010,
Pubmed
Romero,
Expression cloning and characterization of a renal electrogenic Na+/HCO3- cotransporter.
1997,
Pubmed
,
Xenbase
Romero,
The SLC4 family of HCO 3 - transporters.
2004,
Pubmed
Russell,
New insights into the structural mechanisms of the COPII coat.
2010,
Pubmed
Sassani,
Functional characterization of NBC4: a new electrogenic sodium-bicarbonate cotransporter.
2002,
Pubmed
Srinivasan,
Nicotine up-regulates alpha4beta2 nicotinic receptors and ER exit sites via stoichiometry-dependent chaperoning.
2011,
Pubmed
Suzuki,
Defective membrane expression of the Na(+)-HCO(3)(-) cotransporter NBCe1 is associated with familial migraine.
2010,
Pubmed
,
Xenbase
Toye,
The human NBCe1-A mutant R881C, associated with proximal renal tubular acidosis, retains function but is mistargeted in polarized renal epithelia.
2006,
Pubmed
,
Xenbase
Virkki,
Functional characterization of human NBC4 as an electrogenic Na+-HCO cotransporter (NBCe2).
2002,
Pubmed
,
Xenbase
Wang,
The Na+-driven Cl-/HCO3- exchanger. Cloning, tissue distribution, and functional characterization.
2000,
Pubmed
,
Xenbase
Wendeler,
Role of Sec24 isoforms in selective export of membrane proteins from the endoplasmic reticulum.
2007,
Pubmed
Zhu,
Structural and functional characterization of the C-terminal transmembrane region of NBCe1-A.
2010,
Pubmed
Zhu,
Novel topology in C-terminal region of the human plasma membrane anion exchanger, AE1.
2003,
Pubmed
