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.
J Biol Chem
2009 Oct 09;28441:28306-18. doi: 10.1074/jbc.M109.001669.
Show Gene links
Show Anatomy links
Slc26a9 is inhibited by the R-region of the cystic fibrosis transmembrane conductance regulator via the STAS domain.
Chang MH
,
Plata C
,
Sindic A
,
Ranatunga WK
,
Chen AP
,
Zandi-Nejad K
,
Chan KW
,
Thompson J
,
Mount DB
,
Romero MF
.
???displayArticle.abstract???
SLC26 proteins function as anion exchangers, channels, and sensors. Previous cellular studies have shown that Slc26a3 and Slc26a6 interact with the R-region of the cystic fibrosis transmembrane conductance regulator (CFTR), (R)CFTR, via the Slc26-STAS (sulfate transporter anti-sigma) domain, resulting in mutual transport activation. We recently showed that Slc26a9 has both nCl(-)-HCO(3)(-) exchanger and Cl(-) channel function. In this study, we show that the purified STAS domain of Slc26a9 (a9STAS) binds purified (R)CFTR. When Slc26a9 and (R)CFTR fragments are co-expressed in Xenopus oocytes, both Slc26a9-mediated nCl(-)-HCO(3)(-) exchange and Cl(-) currents are almost fully inhibited. Deletion of the Slc26a9 STAS domain (a9-DeltaSTAS) virtually eliminated the Cl(-) currents with only a modest affect on nCl(-)-HCO(3)(-) exchange activity. Co-expression of a9-DeltaSTAS and the (R)CFTR fragment did not alter the residual a9-DeltaSTAS function. Replacing the Slc26a9 STAS domain with the Slc26a6 STAS domain (a6-a9-a6) does not change Slc26a9 function and is no longer inhibited by (R)CFTR. These data indicate that the Slc26a9-STAS domain, like other Slc26-STAS domains, binds CFTR in the R-region. However, unlike previously reported data, this binding interaction inhibits Slc26a9 ion transport activity. These results imply that Slc26-STAS domains may all interact with (R)CFTR but that the physiological outcome is specific to differing Slc26 proteins, allowing for dynamic and acute fine tuning of ion transport for various epithelia.
Aronson,
Essential roles of CFEX-mediated Cl(-)-oxalate exchange in proximal tubule NaCl transport and prevention of urolithiasis.
2006, Pubmed,
Xenbase
Aronson,
Essential roles of CFEX-mediated Cl(-)-oxalate exchange in proximal tubule NaCl transport and prevention of urolithiasis.
2006,
Pubmed
,
Xenbase
Baker,
CFTR regulatory region interacts with NBD1 predominantly via multiple transient helices.
2007,
Pubmed
Bertrand,
SLC26A9 is a constitutively active, CFTR-regulated anion conductance in human bronchial epithelia.
2009,
Pubmed
Bissig,
Functional expression cloning of the canalicular sulfate transport system of rat hepatocytes.
1994,
Pubmed
,
Xenbase
Cai,
Mutational analysis of the DTDST gene in a fetus with achondrogenesis type 1B.
1998,
Pubmed
Chan,
Severed molecules functionally define the boundaries of the cystic fibrosis transmembrane conductance regulator's NH(2)-terminal nucleotide binding domain.
2000,
Pubmed
,
Xenbase
Chang,
Entry to "formula tunnel" revealed by SLC4A4 human mutation and structural model.
2008,
Pubmed
,
Xenbase
Chang,
Slc26a9--anion exchanger, channel and Na+ transporter.
2009,
Pubmed
,
Xenbase
Chernova,
Acute regulation of the SLC26A3 congenital chloride diarrhoea anion exchanger (DRA) expressed in Xenopus oocytes.
2003,
Pubmed
,
Xenbase
Choate,
WNK1, a kinase mutated in inherited hypertension with hyperkalemia, localizes to diverse Cl- -transporting epithelia.
2003,
Pubmed
Coyle,
Molecular analysis of the PDS gene in Pendred syndrome.
1998,
Pubmed
Dallos,
Prestin-based outer hair cell motility is necessary for mammalian cochlear amplification.
2008,
Pubmed
Detro-Dassen,
Conserved dimeric subunit stoichiometry of SLC26 multifunctional anion exchangers.
2008,
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
Donnelly,
An expression vector tailored for large-scale, high-throughput purification of recombinant proteins.
2006,
Pubmed
Dorwart,
SLC26A9 is a Cl(-) channel regulated by the WNK kinases.
2007,
Pubmed
,
Xenbase
Dorwart,
Congenital chloride-losing diarrhea causing mutations in the STAS domain result in misfolding and mistrafficking of SLC26A3.
2008,
Pubmed
Drexl,
The role of prestin in the generation of electrically evoked otoacoustic emissions in mice.
2008,
Pubmed
Everett,
Targeted disruption of mouse Pds provides insight about the inner-ear defects encountered in Pendred syndrome.
2001,
Pubmed
Everett,
Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS).
1997,
Pubmed
Huth,
Design of an expression system for detecting folded protein domains and mapping macromolecular interactions by NMR.
1997,
Pubmed
Hästbacka,
Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias.
1996,
Pubmed
Hästbacka,
Identification of the Finnish founder mutation for diastrophic dysplasia (DTD).
1999,
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,
Identification of seven novel mutations including the first two genomic rearrangements in SLC26A3 mutated in congenital chloride diarrhea.
2001,
Pubmed
Ishiguro,
Effect of Slc26a6 deletion on apical Cl-/HCO3- exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct.
2007,
Pubmed
Jiang,
Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6.
2006,
Pubmed
Kahle,
WNK4 regulates the balance between renal NaCl reabsorption and K+ secretion.
2003,
Pubmed
,
Xenbase
Kahle,
Paracellular Cl- permeability is regulated by WNK4 kinase: insight into normal physiology and hypertension.
2004,
Pubmed
Kahle,
Molecular physiology of the WNK kinases.
2008,
Pubmed
Ko,
A molecular mechanism for aberrant CFTR-dependent HCO(3)(-) transport in cystic fibrosis.
2002,
Pubmed
Ko,
Gating of CFTR by the STAS domain of SLC26 transporters.
2004,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Liu,
Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss.
2003,
Pubmed
Lohi,
Isoforms of SLC26A6 mediate anion transport and have functional PDZ interaction domains.
2003,
Pubmed
,
Xenbase
Loriol,
Characterization of SLC26A9, facilitation of Cl(-) transport by bicarbonate.
2008,
Pubmed
,
Xenbase
Monico,
Phenotypic and functional analysis of human SLC26A6 variants in patients with familial hyperoxaluria and calcium oxalate nephrolithiasis.
2008,
Pubmed
,
Xenbase
Mount,
The SLC26 gene family of multifunctional anion exchangers.
2004,
Pubmed
Mäkelä,
SLC26A3 mutations in congenital chloride diarrhea.
2002,
Pubmed
Mäkelä,
Mutational analysis of the human SLC26A8 gene: exclusion as a candidate for male infertility due to primary spermatogenic failure.
2005,
Pubmed
Romero,
Cloning and characterization of a Na+-driven anion exchanger (NDAE1). A new bicarbonate transporter.
2000,
Pubmed
,
Xenbase
Romero,
Cloning and functional expression of rNBC, an electrogenic Na(+)-HCO3- cotransporter from rat kidney.
1998,
Pubmed
,
Xenbase
Romero,
Physiology of electrogenic SLC26 paralogues.
2006,
Pubmed
,
Xenbase
Rossi,
In vitro proteoglycan sulfation derived from sulfhydryl compounds in sulfate transporter chondrodysplasias.
2003,
Pubmed
Rossi,
Phenotypic and genotypic overlap between atelosteogenesis type 2 and diastrophic dysplasia.
1996,
Pubmed
Royaux,
Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion.
2001,
Pubmed
Sciortino,
Cation and voltage dependence of rat kidney electrogenic Na(+)-HCO(-)(3) cotransporter, rkNBC, expressed in oocytes.
1999,
Pubmed
,
Xenbase
Seidler,
Sodium and chloride absorptive defects in the small intestine in Slc26a6 null mice.
2008,
Pubmed
Shcheynikov,
Dynamic control of cystic fibrosis transmembrane conductance regulator Cl(-)/HCO3(-) selectivity by external Cl(-).
2004,
Pubmed
,
Xenbase
Shcheynikov,
Regulatory interaction between CFTR and the SLC26 transporters.
2006,
Pubmed
,
Xenbase
Shibagaki,
The role of the STAS domain in the function and biogenesis of a sulfate transporter as probed by random mutagenesis.
2006,
Pubmed
Singh,
Fructose-induced hypertension: essential role of chloride and fructose absorbing transporters PAT1 and Glut5.
2008,
Pubmed
Soleimani,
The role of SLC26A6-mediated chloride/oxalate exchange in causing susceptibility to nephrolithiasis.
2008,
Pubmed
Touré,
The testis anion transporter 1 (Slc26a8) is required for sperm terminal differentiation and male fertility in the mouse.
2007,
Pubmed
Wagner,
Regulation of the expression of the Cl-/anion exchanger pendrin in mouse kidney by acid-base status.
2002,
Pubmed
Wang,
Renal and intestinal transport defects in Slc26a6-null mice.
2005,
Pubmed
Wang,
Slc26a6 regulates CFTR activity in vivo to determine pancreatic duct HCO3- secretion: relevance to cystic fibrosis.
2006,
Pubmed
Wilson,
Human hypertension caused by mutations in WNK kinases.
2001,
Pubmed
Wu,
Hearing threshold elevation precedes hair-cell loss in prestin knockout mice.
2004,
Pubmed
Xie,
Molecular characterization of the murine Slc26a6 anion exchanger: functional comparison with Slc26a1.
2002,
Pubmed
,
Xenbase
Xu,
SLC26A9 is expressed in gastric surface epithelial cells, mediates Cl-/HCO3- exchange, and is inhibited by NH4+.
2005,
Pubmed
Xu,
Deletion of the chloride transporter Slc26a9 causes loss of tubulovesicles in parietal cells and impairs acid secretion in the stomach.
2008,
Pubmed
,
Xenbase
Zheng,
Prestin is the motor protein of cochlear outer hair cells.
2000,
Pubmed
