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Pflugers Arch
2016 Aug 01;4688:1311-32. doi: 10.1007/s00424-016-1823-8.
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Extracellular Cl(-) regulates human SO4 (2-)/anion exchanger SLC26A1 by altering pH sensitivity of anion transport.
Wu M, Heneghan JF, Vandorpe DH, Escobar LI, Wu BL, Alper SL.
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Genetic deficiency of the SLC26A1 anion exchanger in mice is known to be associated with hyposulfatemia and hyperoxaluria with nephrolithiasis, but many aspects of human SLC26A1 function remain to be explored. We report here the functional characterization of human SLC26A1, a 4,4'-diisothiocyanato-2,2'-stilbenedisulfonic acid (DIDS)-sensitive, electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, bicarbonate, thiosulfate, and (with divergent properties) chloride. Human SLC26A1-mediated anion exchange differs from that of its rodent orthologs in its stimulation by alkaline pHo and inhibition by acidic pHo but not pHi and in its failure to transport glyoxylate. SLC26A1-mediated transport of sulfate and oxalate is highly dependent on allosteric activation by extracellular chloride or non-substrate anions. Extracellular chloride stimulates apparent V max of human SLC26A1-mediated sulfate uptake by conferring a 2-log decrease in sensitivity to inhibition by extracellular protons, without changing transporter affinity for extracellular sulfate. In contrast to SLC26A1-mediated sulfate transport, SLC26A1-associated chloride transport is activated by acid pHo, shows reduced sensitivity to DIDS, and exhibits cation dependence of its DIDS-insensitive component. Human SLC26A1 resembles SLC26 paralogs in its inhibition by phorbol ester activation of protein kinase C (PKC), which differs in its undiminished polypeptide abundance at or near the oocyte surface. Mutation of SLC26A1 residues corresponding to candidate anion binding site-associated residues in avian SLC26A5/prestin altered anion transport in patterns resembling those of prestin. However, rare SLC26A1 polymorphic variants from a patient with renal Fanconi Syndrome and from a patient with nephrolithiasis/calcinosis exhibited no loss-of-function phenotypes consistent with disease pathogenesis.
Alper,
The SLC26 gene family of anion transporters and channels.
2013, Pubmed
Alper,
The SLC26 gene family of anion transporters and channels.
2013,
Pubmed Aronson,
Mechanisms of chloride transport in the proximal tubule.
1997,
Pubmed Babu,
Structure of a SLC26 anion transporter STAS domain in complex with acyl carrier protein: implications for E. coli YchM in fatty acid metabolism.
2010,
Pubmed Barbosa,
Clinical and molecular characterization of Diastrophic Dysplasia in the Portuguese population.
2011,
Pubmed Bian,
Real time measures of prestin charge and fluorescence during plasma membrane trafficking reveal sub-tetrameric activity.
2013,
Pubmed Biber,
Renal handling of phosphate and sulfate.
2014,
Pubmed Bissig,
Functional expression cloning of the canalicular sulfate transport system of rat hepatocytes.
1994,
Pubmed
,
Xenbase Bizhanova,
Genetics and phenomics of Pendred syndrome.
2010,
Pubmed Blackman,
Genetic modifiers of cystic fibrosis-related diabetes.
2013,
Pubmed Breljak,
In female rats, ethylene glycol treatment elevates protein expression of hepatic and renal oxalate transporter sat-1 (Slc26a1) without inducing hyperoxaluria.
2015,
Pubmed Brzica,
The liver and kidney expression of sulfate anion transporter sat-1 in rats exhibits male-dominant gender differences.
2009,
Pubmed Brzica,
Oxalate: from the environment to kidney stones.
2013,
Pubmed Chang,
Slc26a9--anion exchanger, channel and Na+ transporter.
2009,
Pubmed
,
Xenbase Compton,
Low resolution structure of a bacterial SLC26 transporter reveals dimeric stoichiometry and mobile intracellular domains.
2011,
Pubmed Cordat,
Structure, function, and trafficking of SLC4 and SLC26 anion transporters.
2014,
Pubmed Dawson,
Human SLC26A1 gene variants: a pilot study.
2013,
Pubmed Dawson,
Sulphate in pregnancy.
2015,
Pubmed Dawson,
Urolithiasis and hepatotoxicity are linked to the anion transporter Sat1 in mice.
2010,
Pubmed Dawson,
Sulfate in fetal development.
2011,
Pubmed Dick,
Proteoglycan synthesis and Golgi organization in polarized epithelial cells.
2012,
Pubmed Dirami,
Missense mutations in SLC26A8, encoding a sperm-specific activator of CFTR, are associated with human asthenozoospermia.
2013,
Pubmed Freel,
Hyperoxaluric rats do not exhibit alterations in renal expression patterns of Slc26a1 (SAT1) mRNA or protein.
2012,
Pubmed Geertsma,
Structure of a prokaryotic fumarate transporter reveals the architecture of the SLC26 family.
2015,
Pubmed Glatt,
Pharmacogenetics of soluble sulfotransferases (SULTs).
2004,
Pubmed Good,
Hydrogen ion buffers for biological research.
1966,
Pubmed Gorbunov,
Molecular architecture and the structural basis for anion interaction in prestin and SLC26 transporters.
2014,
Pubmed Habuchi,
Sulfation pattern in glycosaminoglycan: does it have a code?
2004,
Pubmed Haila,
SLC26A2 (diastrophic dysplasia sulfate transporter) is expressed in developing and mature cartilage but also in other tissues and cell types.
2001,
Pubmed Hassan,
Regulation of anion exchanger Slc26a6 by protein kinase C.
2007,
Pubmed
,
Xenbase Heneghan,
Regulated transport of sulfate and oxalate by SLC26A2/DTDST.
2010,
Pubmed
,
Xenbase HIERHOLZER,
Stop-flow analysis of renal reabsorption and excretion of sulfate in the dog.
1960,
Pubmed Jia,
Identification of the Human SULT Enzymes Involved in the Metabolism of Rotigotine.
2016,
Pubmed Jiang,
Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6.
2006,
Pubmed Jun,
Pore dilatation increases the bicarbonate permeability of CFTR, ANO1 and glycine receptor anion channels.
2016,
Pubmed Karinou,
The Escherichia coli SLC26 homologue YchM (DauA) is a C(4)-dicarboxylic acid transporter.
2013,
Pubmed Karniski,
Immunolocalization of sat-1 sulfate/oxalate/bicarbonate anion exchanger in the rat kidney.
1998,
Pubmed Knight,
Oxalate secretion in the rat proximal tubule.
1981,
Pubmed Ko,
Sat1 is dispensable for active oxalate secretion in mouse duodenum.
2012,
Pubmed Krick,
Ability of sat-1 to transport sulfate, bicarbonate, or oxalate under physiological conditions.
2009,
Pubmed
,
Xenbase Kuo,
Oxalate transport via the sulfate/HCO3 exchanger in rabbit renal basolateral membrane vesicles.
1988,
Pubmed Lee,
The mouse sulfate anion transporter gene Sat1 (Slc26a1): cloning, tissue distribution, gene structure, functional characterization, and transcriptional regulation thyroid hormone.
2003,
Pubmed
,
Xenbase Levitt,
Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa.
1999,
Pubmed Li,
N-glycosylation and topology of the human SLC26 family of anion transport membrane proteins.
2014,
Pubmed Liu,
Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss.
2003,
Pubmed Loriol,
Characterization of SLC26A9, facilitation of Cl(-) transport by bicarbonate.
2008,
Pubmed
,
Xenbase Magen,
A loss-of-function mutation in NaPi-IIa and renal Fanconi's syndrome.
2010,
Pubmed
,
Xenbase Markovich,
Physiological roles of renal anion transporters NaS1 and Sat1.
2011,
Pubmed Markovich,
Slc13a1 and Slc26a1 KO models reveal physiological roles of anion transporters.
2012,
Pubmed Morris,
Serum concentration and renal excretion by normal adults of inorganic sulfate after acetaminophen, ascorbic acid, or sodium sulfate.
1983,
Pubmed Nakada,
Roles of Slc13a1 and Slc26a1 sulfate transporters of eel kidney in sulfate homeostasis and osmoregulation in freshwater.
2005,
Pubmed
,
Xenbase Nakanishi,
Association of hyperhomocysteinemia with plasma sulfate and urine sulfate excretion in patients with progressive renal disease.
2002,
Pubmed Nazzal,
Enteric hyperoxaluria: an important cause of end-stage kidney disease.
2016,
Pubmed Nigwekar,
Sodium thiosulfate therapy for calcific uremic arteriolopathy.
2013,
Pubmed Ohana,
Diverse transport modes by the solute carrier 26 family of anion transporters.
2009,
Pubmed Ohana,
Solute carrier family 26 member a2 (Slc26a2) protein functions as an electroneutral SOFormula/OH-/Cl- exchanger regulated by extracellular Cl-.
2012,
Pubmed
,
Xenbase Okonkwo,
A pilot study of the effect of sodium thiosulfate on urinary lithogenicity and associated metabolic acid load in non-stone formers and stone formers with hypercalciuria.
2013,
Pubmed Park,
Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion.
2010,
Pubmed Planelles,
Chloride transport in the renal proximal tubule.
2004,
Pubmed Quondamatteo,
Localization of the sulfate/anion exchanger in the rat liver.
2006,
Pubmed Regeer,
A dileucine motif targets the sulfate anion transporter sat-1 to the basolateral membrane in renal cell lines.
2004,
Pubmed
,
Xenbase Regeer,
Characterization of the human sulfate anion transporter (hsat-1) protein and gene (SAT1; SLC26A1).
2003,
Pubmed
,
Xenbase Reimold,
Pendrin function and regulation in Xenopus oocytes.
2011,
Pubmed
,
Xenbase Reimold,
Congenital chloride-losing diarrhea in a Mexican child with the novel homozygous SLC26A3 mutation G393W.
2015,
Pubmed
,
Xenbase Romero,
Physiology of electrogenic SLC26 paralogues.
2006,
Pubmed
,
Xenbase Rungta,
The cellular mechanisms of neuronal swelling underlying cytotoxic edema.
2015,
Pubmed Salomon,
Generation and functional characterization of epithelial cells with stable expression of SLC26A9 Cl- channels.
2016,
Pubmed Santer,
Familial renal glucosuria and SGLT2: from a mendelian trait to a therapeutic target.
2010,
Pubmed Satoh,
Functional analysis of diastrophic dysplasia sulfate transporter. Its involvement in growth regulation of chondrocytes mediated by sulfated proteoglycans.
1998,
Pubmed
,
Xenbase Schnedler,
Glyoxylate is a substrate of the sulfate-oxalate exchanger, sat-1, and increases its expression in HepG2 cells.
2011,
Pubmed
,
Xenbase Senekjian,
Oxalate transport by proximal tubule of the rabbit kidney.
1982,
Pubmed Shcheynikov,
Dynamic control of cystic fibrosis transmembrane conductance regulator Cl(-)/HCO3(-) selectivity by external Cl(-).
2004,
Pubmed
,
Xenbase Shcheynikov,
Intracellular Cl- as a signaling ion that potently regulates Na+/HCO3- transporters.
2015,
Pubmed Srinivasan,
Functional characterization of solute carrier (SLC) 26/sulfate permease (SulP) proteins in membrane mimetic systems.
2016,
Pubmed Stewart,
Regulation of AE2 anion exchanger by intracellular pH: critical regions of the NH(2)-terminal cytoplasmic domain.
2001,
Pubmed
,
Xenbase Subramanian,
Glyoxalate reductase/hydroxypyruvate reductase interacts with the sodium-dependent vitamin C transporter-1 to regulate cellular vitamin C homeostasis.
2013,
Pubmed Sun,
Multiple apical plasma membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis.
2012,
Pubmed Wang,
Prestin forms oligomer with four mechanically independent subunits.
2010,
Pubmed Wangemann,
Mouse models for pendrin-associated loss of cochlear and vestibular function.
2013,
Pubmed Wedenoja,
Update on SLC26A3 mutations in congenital chloride diarrhea.
2011,
Pubmed Weinstein,
Flow-dependent transport in a mathematical model of rat proximal tubule.
2007,
Pubmed Xie,
Molecular characterization of the murine Slc26a6 anion exchanger: functional comparison with Slc26a1.
2002,
Pubmed
,
Xenbase Xu,
Deletion of the chloride transporter slc26a7 causes distal renal tubular acidosis and impairs gastric acid secretion.
2009,
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 Yin,
SLC26A Gene Family Participate in pH Regulation during Enamel Maturation.
2015,
Pubmed
