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J Physiol
2003 May 15;549Pt 1:3-19. doi: 10.1113/jphysiol.2003.039818.
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Acute regulation of the SLC26A3 congenital chloride diarrhoea anion exchanger (DRA) expressed in Xenopus oocytes.
Chernova MN
,
Jiang L
,
Shmukler BE
,
Schweinfest CW
,
Blanco P
,
Freedman SD
,
Stewart AK
,
Alper SL
.
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Mutations in the human SLC26A3 gene, also known as down-regulated in adenoma (hDRA), cause autosomal recessive congenital chloride-losing diarrhoea (CLD). hDRA expressed in Xenopus oocytes mediated bidirectional Cl--Cl- and Cl--HCO3- exchange. In contrast, transport of oxalate was low, and transport of sulfate and of butyrate was undetectable. Two CLD missense disease mutants of hDRA were nonfunctional in oocytes. Truncation of up to 44 C-terminal amino acids from the putatively cytoplasmic C-terminal hydrophilic domain left transport function unimpaired, but deletion of the adjacent STAS (sulfate transporter anti-sigma factor antagonist) domain abolished function. hDRA-mediated Cl- transport was insensitive to changing extracellular pH, but was inhibited by intracellular acidification and activated by NH4+ at acidifying concentrations. These regulatory responses did not require the presence of either hDRA's N-terminal cytoplasmic tail or its 44 C-terminal amino acids, but they did require more proximate residues of the C-terminal cytoplasmic domain. Although only weakly sensitive to inhibition by stilbenes, hDRA was inhibited with two orders of magnitude greater potency by the anti-inflammatory drugs niflumate and tenidap. cAMP-insensitive Cl--HCO3- exchange mediated by hDRA gained modest cAMP sensitivity when co-expressed with cystic fibrosis transmembrane conductance regulator (CFTR). Despite the absence of hDRA transcripts in human cell lines derived from CFTR patients, DRA mRNA was present at wild-type levels in proximal colon and nearly so in the distal ileum of CFTR(-/-) mice. Thus, pharmacological modulation of DRA might be a useful adjunct treatment of cystic fibrosis.
Aichbichler,
Proton-pump inhibition of gastric chloride secretion in congenital chloridorrhea.
1997, Pubmed
Aichbichler,
Proton-pump inhibition of gastric chloride secretion in congenital chloridorrhea.
1997,
Pubmed
Alper,
Genetic diseases of acid-base transporters.
2002,
Pubmed
Antalis,
Down-regulation of the down-regulated in adenoma (DRA) gene correlates with colon tumor progression.
1998,
Pubmed
Aravind,
The STAS domain - a link between anion transporters and antisigma-factor antagonists.
2000,
Pubmed
Bennekou,
Volume control in sickle cells is facilitated by the novel anion conductance inhibitor NS1652.
2000,
Pubmed
Bissig,
Functional expression cloning of the canalicular sulfate transport system of rat hepatocytes.
1994,
Pubmed
,
Xenbase
Brouillard,
NF-kappa B mediates up-regulation of CFTR gene expression in Calu-3 cells by interleukin-1beta.
2001,
Pubmed
Byeon,
Human DRA functions as a sulfate transporter in Sf9 insect cells.
1998,
Pubmed
Byeon,
The down-regulated in adenoma (DRA) gene encodes an intestine-specific membrane glycoprotein.
1996,
Pubmed
Casula,
A dominant negative mutant of the KCC1 K-Cl cotransporter: both N- and C-terminal cytoplasmic domains are required for K-Cl cotransport activity.
2001,
Pubmed
,
Xenbase
Chapman,
The colon anion transporter, down-regulated in adenoma, induces growth suppression that is abrogated by E1A.
2002,
Pubmed
Chernova,
Structure-function relationships of AE2 regulation by Ca(i)(2+)-sensitive stimulators NH(4+) and hypertonicity.
2003,
Pubmed
,
Xenbase
Chernova,
Electrogenic sulfate/chloride exchange in Xenopus oocytes mediated by murine AE1 E699Q.
1997,
Pubmed
,
Xenbase
Chmiel,
The role of inflammation in the pathophysiology of CF lung disease.
2002,
Pubmed
Choi,
Aberrant CFTR-dependent HCO3- transport in mutations associated with cystic fibrosis.
2001,
Pubmed
Chu,
Non-ionic diffusion and carrier-mediated transport drive extracellullar pH regulation of mouse colonic crypts.
1996,
Pubmed
Devor,
Ibuprofen inhibits cystic fibrosis transmembrane conductance regulator-mediated Cl- secretion.
1998,
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
Everett,
Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS).
1997,
Pubmed
Everett,
A family of mammalian anion transporters and their involvement in human genetic diseases.
1999,
Pubmed
Freedman,
A membrane lipid imbalance plays a role in the phenotypic expression of cystic fibrosis in cftr(-/-) mice.
1999,
Pubmed
Goss,
Role of JNK in hypertonic activation of Cl(-)-dependent Na(+)/H(+) exchange in Xenopus oocytes.
2001,
Pubmed
,
Xenbase
Greeley,
Downregulated in adenoma and putative anion transporter are regulated by CFTR in cultured pancreatic duct cells.
2001,
Pubmed
Grubb,
Pathophysiology of gene-targeted mouse models for cystic fibrosis.
1999,
Pubmed
Haila,
The congenital chloride diarrhea gene is expressed in seminal vesicle, sweat gland, inflammatory colon epithelium, and in some dysplastic colon cells.
2000,
Pubmed
Humphreys,
Hypertonic activation of AE2 anion exchanger in Xenopus oocytes via NHE-mediated intracellular alkalinization.
1995,
Pubmed
,
Xenbase
Hästbacka,
The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping.
1994,
Pubmed
Höglund,
Clustering of private mutations in the congenital chloride diarrhea/down-regulated in adenoma gene.
1998,
Pubmed
Höglund,
Distinct outcomes of chloride diarrhoea in two siblings with identical genetic background of the disease: implications for early diagnosis and treatment.
2001,
Pubmed
Höglund,
Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea.
1996,
Pubmed
Jacob,
Down-regulated in adenoma mediates apical Cl-/HCO3- exchange in rabbit, rat, and human duodenum.
2002,
Pubmed
Jiang,
Specificity of anion exchange mediated by mouse Slc26a6.
2002,
Pubmed
,
Xenbase
Karniski,
Immunolocalization of sat-1 sulfate/oxalate/bicarbonate anion exchanger in the rat kidney.
1998,
Pubmed
Kere,
Genetic Disorders of Membrane Transport III. Congenital chloride diarrhea.
1999,
Pubmed
Knauf,
Identification of a chloride-formate exchanger expressed on the brush border membrane of renal proximal tubule cells.
2001,
Pubmed
,
Xenbase
Ko,
A molecular mechanism for aberrant CFTR-dependent HCO(3)(-) transport in cystic fibrosis.
2002,
Pubmed
Lamprecht,
The down regulated in adenoma (dra) gene product binds to the second PDZ domain of the NHE3 kinase A regulatory protein (E3KARP), potentially linking intestinal Cl-/HCO3- exchange to Na+/H+ exchange.
2002,
Pubmed
Lee,
Regulation of Cl-/ HCO3- exchange by cystic fibrosis transmembrane conductance regulator expressed in NIH 3T3 and HEK 293 cells.
1999,
Pubmed
Loh,
Effect of S20787, a novel Cl--HCO3- exchange inhibitor, on intracellular pH regulation in guinea pig ventricular myocytes.
2001,
Pubmed
Lohi,
Mapping of five new putative anion transporter genes in human and characterization of SLC26A6, a candidate gene for pancreatic anion exchanger.
2000,
Pubmed
Lohi,
Functional characterization of three novel tissue-specific anion exchangers SLC26A7, -A8, and -A9.
2002,
Pubmed
,
Xenbase
Lohi,
Upregulation of CFTR expression but not SLC26A3 and SLC9A3 in ulcerative colitis.
2002,
Pubmed
Markovich,
Physiological roles and regulation of mammalian sulfate transporters.
2001,
Pubmed
Markovich,
Expression of rat renal sulfate transport systems in Xenopus laevis oocytes. Functional characterization and molecular identification.
1994,
Pubmed
,
Xenbase
McNiff,
Reduction of intracellular pH by tenidap. Involvement of cellular anion transporters in the pH change.
1995,
Pubmed
Melvin,
Mouse down-regulated in adenoma (DRA) is an intestinal Cl(-)/HCO(3)(-) exchanger and is up-regulated in colon of mice lacking the NHE3 Na(+)/H(+) exchanger.
1999,
Pubmed
Moseley,
Downregulated in adenoma gene encodes a chloride transporter defective in congenital chloride diarrhea.
1999,
Pubmed
,
Xenbase
Oliver,
Intracellular anions as the voltage sensor of prestin, the outer hair cell motor protein.
2001,
Pubmed
Pratha,
Identification of transport abnormalities in duodenal mucosa and duodenal enterocytes from patients with cystic fibrosis.
2000,
Pubmed
Rajendran,
Apical membrane Cl-butyrate exchange: mechanism of short chain fatty acid stimulation of active chloride absorption in rat distal colon.
1994,
Pubmed
Romero,
Expression cloning and characterization of a renal electrogenic Na+/HCO3- cotransporter.
1997,
Pubmed
,
Xenbase
Royaux,
Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion.
2001,
Pubmed
Satoh,
Functional analysis of diastrophic dysplasia sulfate transporter. Its involvement in growth regulation of chondrocytes mediated by sulfated proteoglycans.
1998,
Pubmed
,
Xenbase
Schweinfest,
Identification of a colon mucosa gene that is down-regulated in colon adenomas and adenocarcinomas.
1993,
Pubmed
Scott,
Human pendrin expressed in Xenopus laevis oocytes mediates chloride/formate exchange.
2000,
Pubmed
,
Xenbase
Scott,
The Pendred syndrome gene encodes a chloride-iodide transport protein.
1999,
Pubmed
,
Xenbase
Silberg,
The Down regulated in Adenoma (dra) gene encodes an intestine-specific membrane sulfate transport protein.
1995,
Pubmed
,
Xenbase
Simchowitz,
Intracellular pH recovery from alkalinization. Characterization of chloride and bicarbonate transport by the anion exchange system of human neutrophils.
1990,
Pubmed
Snouwaert,
An animal model for cystic fibrosis made by gene targeting.
1992,
Pubmed
Stewart,
Regulation of AE2 anion exchanger by intracellular pH: critical regions of the NH(2)-terminal cytoplasmic domain.
2001,
Pubmed
,
Xenbase
Stewart,
Regulation of AE2-mediated Cl- transport by intracellular or by extracellular pH requires highly conserved amino acid residues of the AE2 NH2-terminal cytoplasmic domain.
2002,
Pubmed
,
Xenbase
Suzuki,
Expression of PDS/Pds, the Pendred syndrome gene, in endometrium.
2002,
Pubmed
Tondelier,
Aspirin and some other nonsteroidal anti-inflammatory drugs inhibit cystic fibrosis transmembrane conductance regulator protein gene expression in T-84 cells.
1999,
Pubmed
Toure,
Tat1, a novel sulfate transporter specifically expressed in human male germ cells and potentially linked to rhogtpase signaling.
2001,
Pubmed
Vincourt,
Molecular cloning of SLC26A7, a novel member of the SLC26 sulfate/anion transporter family, from high endothelial venules and kidney.
2002,
Pubmed
Waldegger,
Cloning and characterization of SLC26A6, a novel member of the solute carrier 26 gene family.
2001,
Pubmed
,
Xenbase
Wang,
Identification of an apical Cl(-)/HCO3(-) exchanger in the small intestine.
2002,
Pubmed
,
Xenbase
Wheat,
CFTR induces the expression of DRA along with Cl(-)/HCO(3)(-) exchange activity in tracheal epithelial cells.
2000,
Pubmed
Xie,
Molecular characterization of the murine Slc26a6 anion exchanger: functional comparison with Slc26a1.
2002,
Pubmed
,
Xenbase
Yang,
Intestinal inflammation reduces expression of DRA, a transporter responsible for congenital chloride diarrhea.
1998,
Pubmed
Zhang,
The cytoplasmic and transmembrane domains of AE2 both contribute to regulation of anion exchange by pH.
1996,
Pubmed
,
Xenbase
Zheng,
Prestin is the motor protein of cochlear outer hair cells.
2000,
Pubmed
