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J Physiol
2008 Aug 15;58616:3813-24. doi: 10.1113/jphysiol.2008.154468.
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The Slc26a4 transporter functions as an electroneutral Cl-/I-/HCO3- exchanger: role of Slc26a4 and Slc26a6 in I- and HCO3- secretion and in regulation of CFTR in the parotid duct.
Shcheynikov N, Yang D, Wang Y, Zeng W, Karniski LP, So I, Wall SM, Muallem S.
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Transcellular Cl(-) and HCO(3)(-) transport is a vital function of secretory epithelia and exit across the luminal membrane is mediated by members of the SLC26 transporters in conjunction with cystic fibrosis transmembrane conductance regulator (CFTR) channel. Typically, secretory epithelia express several SLC26 transporters in the same tissue; however, how their specific function is determined in vivo is not known. In the present work we used the parotid gland duct which expressed Slc26a4 and Slc26a6 and the model systems of Slc26a4(-/-) and Slc26a6(-/-) mice to study the role and regulation of these SLC26 transporters. We examined the transport modes of SLC26A4 expressed in Xenopus oocytes and report that SLC26A4 functions as a coupled, electroneutral I(-)/Cl(-), I(-)/HCO(3)(-) and Cl(-)/HCO(3)(-) exchanger with 1: 1 stoichiometry, with I(-) as the preferred anion. In the duct, Slc26a4 is expressed in the luminal membrane and mainly mediates I(-) secretion with minimal role in luminal HCO(3)(-) transport. By contrast, Slc26a6 mediates luminal Cl(-)/HCO(3)(-) exchange activity with minimal role in I(-) secretion. Furthermore, silencing of CFTR altered Cl(-)/HCO(3)(-) exchange by Slc26a6, but had no effect on I(-) secretion by Slc26a4. Accordingly, deletion of Slc26a6, but not deletion of Slc26a4, results in dysregulation of CFTR. These findings provide the first evidence for a selective role of the SLC26 transporters expressed in the same tissue in epithelial anion transport and suggest that transport specificity is achieved by both the properties of the transporters and the composition of the complexes they form.
Ashton,
Effect of vasoactive intestinal peptide, bombesin and substance P on fluid secretion by isolated rat pancreatic ducts.
1990, Pubmed
Ashton,
Effect of vasoactive intestinal peptide, bombesin and substance P on fluid secretion by isolated rat pancreatic ducts.
1990,
Pubmed Baumgarten,
Intracellular chloride activity in mammalian ventricular muscle.
1981,
Pubmed Dorwart,
The solute carrier 26 family of proteins in epithelial ion transport.
2008,
Pubmed Dorwart,
SLC26A9 is a Cl(-) channel regulated by the WNK kinases.
2007,
Pubmed
,
Xenbase Dossena,
The expression of wild-type pendrin (SLC26A4) in human embryonic kidney (HEK 293 Phoenix) cells leads to the activation of cationic currents.
2005,
Pubmed Everett,
Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS).
1997,
Pubmed Jiang,
Specificity of anion exchange mediated by mouse Slc26a6.
2002,
Pubmed
,
Xenbase Josefsson,
Sodium/iodide-symporter: distribution in different mammals and role in entero-thyroid circulation of iodide.
2002,
Pubmed Ketchum,
Characterization of the adenosinetriphosphatase and transport activities of purified cystic fibrosis transmembrane conductance regulator.
2004,
Pubmed Kim,
SLC26A7 is a Cl- channel regulated by intracellular pH.
2005,
Pubmed
,
Xenbase 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 Kogai,
Enhancement of sodium/iodide symporter expression in thyroid and breast cancer.
2006,
Pubmed Kopelman,
Impaired chloride secretion, as well as bicarbonate secretion, underlies the fluid secretory defect in the cystic fibrosis pancreas.
1988,
Pubmed Mandel,
Radioactive iodine and the salivary glands.
2003,
Pubmed Markovich,
Specificity and regulation of renal sulfate transporters.
2007,
Pubmed Melvin,
Regulation of fluid and electrolyte secretion in salivary gland acinar cells.
2005,
Pubmed Petersen,
Chronic pancreatitis and maldigestion.
2002,
Pubmed Scott,
The Pendred syndrome gene encodes a chloride-iodide transport protein.
1999,
Pubmed
,
Xenbase Shcheynikov,
Coupling modes and stoichiometry of Cl-/HCO3- exchange by slc26a3 and slc26a6.
2006,
Pubmed
,
Xenbase Soleimani,
Pendrin: an apical Cl-/OH-/HCO3- exchanger in the kidney cortex.
2001,
Pubmed Steward,
Mechanisms of bicarbonate secretion in the pancreatic duct.
2005,
Pubmed Wall,
Recent advances in our understanding of intercalated cells.
2005,
Pubmed Wang,
Slc26a6 regulates CFTR activity in vivo to determine pancreatic duct HCO3- secretion: relevance to cystic fibrosis.
2006,
Pubmed Wangemann,
Loss of cochlear HCO3- secretion causes deafness via endolymphatic acidification and inhibition of Ca2+ reabsorption in a Pendred syndrome mouse model.
2007,
Pubmed Xie,
Molecular characterization of the murine Slc26a6 anion exchanger: functional comparison with Slc26a1.
2002,
Pubmed
,
Xenbase Yoshida,
Mechanism of iodide/chloride exchange by pendrin.
2004,
Pubmed Zeng,
Membrane-specific regulation of Cl- channels by purinergic receptors in rat submandibular gland acinar and duct cells.
1997,
Pubmed
