Skip to main content
SpringerLink
Log in

Extracellular Cl− regulates human SO4 2−/anion exchanger SLC26A1 by altering pH sensitivity of anion transport

  • Ion channels, receptors and transporters
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

References

  1. Alper SL, Sharma AK (2013) The SLC26 gene family of anion transporters and channels. Mol Asp Med 34:494–515. doi:10.1016/j.mam.2012.07.009

    Article  CAS  Google Scholar 

  2. Aronson PS, Giebisch G (1997) Mechanisms of chloride transport in the proximal tubule. Am J Phys 273:F179–192

    CAS  Google Scholar 

  3. Babu M, Greenblatt JF, Emili A, Strynadka NC, Reithmeier RA, Moraes TF (2010) Structure of a SLC26 anion transporter STAS domain in complex with acyl carrier protein: implications for E. coli YchM in fatty acid metabolism. Structure 18:1450–1462. doi:10.1016/j.str.2010.08.015

    Article  CAS  PubMed  Google Scholar 

  4. Barbosa M, Sousa AB, Medeira A, Lourenco T, Saraiva J, Pinto-Basto J, Soares G, Fortuna AM, Superti-Furga A, Mittaz L, Reis-Lima M, Bonafe L (2011) Clinical and molecular characterization of diastrophic dysplasia in the Portuguese population. Clin Genet 80:550–557. doi:10.1111/j.1399-0004.2010.01595.x

    Article  CAS  PubMed  Google Scholar 

  5. Bian S, Navaratnam D, Santos-Sacchi J (2013) Real time measures of prestin charge and fluorescence during plasma membrane trafficking reveal sub-tetrameric activity. PLoS One 8, e66078. doi:10.1371/journal.pone.0066078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Biber J, Murer H, Mohebbi N, Wagner CA (2014) Renal handling of phosphate and sulfate. Compr Physiol 4:771–792. doi:10.1002/cphy.c120031

    Article  CAS  PubMed  Google Scholar 

  7. Bissig M, Hagenbuch B, Stieger B, Koller T, Meier PJ (1994) Functional expression cloning of the canalicular sulfate transport system of rat hepatocytes. J Biol Chem 269:3017–3021

    CAS  PubMed  Google Scholar 

  8. Bizhanova A, Kopp P (2010) Genetics and phenomics of Pendred syndrome. Mol Cell Endocrinol 322:83–90. doi:10.1016/j.mce.2010.03.006

    Article  CAS  PubMed  Google Scholar 

  9. Blackman SM, Commander CW, Watson C, Arcara KM, Strug LJ, Stonebraker JR, Wright FA, Rommens JM, Sun L, Pace RG, Norris SA, Durie PR, Drumm ML, Knowles MR, Cutting GR (2013) Genetic modifiers of cystic fibrosis-related diabetes. Diabetes 62:3627–3635. doi:10.2337/db13-0510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Breljak D, Brzica H, Vrhovac I, Micek V, Karaica D, Ljubojevic M, Sekovanic A, Jurasovic J, Rasic D, Peraica M, Lovric M, Schnedler N, Henjakovic M, Wegner W, Burckhardt G, Burckhardt BC, Sabolic I (2015) In female rats, ethylene glycol treatment elevates protein expression of hepatic and renal oxalate transporter sat-1 (Slc26a1) without inducing hyperoxaluria. Croat Med J 56:447–459

    Article  PubMed  PubMed Central  Google Scholar 

  11. Brzica H, Breljak D, Burckhardt BC, Burckhardt G, Sabolic I (2013) Oxalate: from the environment to kidney stones. Arh Hig Rada Toksikol 64:609–630. doi:10.2478/10004-1254-64-2013-2428

    Article  CAS  PubMed  Google Scholar 

  12. Brzica H, Breljak D, Krick W, Lovric M, Burckhardt G, Burckhardt BC, Sabolic I (2009) The liver and kidney expression of sulfate anion transporter sat-1 in rats exhibits male-dominant gender differences. Pflugers Arch-Eur J Physiol 457:1381–1392. doi:10.1007/s00424-008-0611-5

    Article  CAS  Google Scholar 

  13. Chang MH, Plata C, Zandi-Nejad K, Sindic A, Sussman CR, Mercado A, Broumand V, Raghuram V, Mount DB, Romero MF (2009) Slc26a9—anion exchanger, channel and Na+ transporter. J Membr Biol 228:125–140. doi:10.1007/s00232-009-9165-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Compton EL, Karinou E, Naismith JH, Gabel F, Javelle A (2011) Low resolution structure of a bacterial SLC26 transporter reveals dimeric stoichiometry and mobile intracellular domains. J Biol Chem 286:27058–27067. doi:10.1074/jbc.M111.244533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cordat E, Reithmeier RA (2014) Structure, function, and trafficking of SLC4 and SLC26 anion transporters. Curr Top Membr 73:1–67. doi:10.1016/b978-0-12-800223-0.00001-3

    Article  CAS  PubMed  Google Scholar 

  16. Dawson PA (2011) Sulfate in fetal development. Semin Cell Dev Biol 22:653–659. doi:10.1016/j.semcdb.2011.03.004

    Article  CAS  PubMed  Google Scholar 

  17. Dawson PA, Elliott A, Bowling FG (2015) Sulphate in pregnancy. Nutrients 7:1594–1606. doi:10.3390/nu7031594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dawson PA, Russell CS, Lee S, McLeay SC, van Dongen JM, Cowley DM, Clarke LA, Markovich D (2010) Urolithiasis and hepatotoxicity are linked to the anion transporter Sat1 in mice. J Clin Invest 120:706–712. doi:10.1172/jci31474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dawson PA, Sim P, Mudge DW, Cowley D (2013) Human SLC26A1 gene variants: a pilot study. The Scientific World Journal 2013:541710. doi:10.1155/2013/541710

    Article  PubMed  PubMed Central  Google Scholar 

  20. Dick G, Akslen-Hoel LK, Grondahl F, Kjos I, Prydz K (2012) Proteoglycan synthesis and Golgi organization in polarized epithelial cells. J Histochem Cytochem Off J Histochem Soc 60:926–935. doi:10.1369/0022155412461256

    Article  Google Scholar 

  21. Dirami T, Rode B, Jollivet M, Da Silva N, Escalier D, Gaitch N, Norez C, Tuffery P, Wolf JP, Becq F, Ray PF, Dulioust E, Gacon G, Bienvenu T, Toure A (2013) Missense mutations in SLC26A8, encoding a sperm-specific activator of CFTR, are associated with human asthenozoospermia. Am J Hum Genet 92:760–766. doi:10.1016/j.ajhg.2013.03.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Freel RW, Hatch M (2012) Hyperoxaluric rats do not exhibit alterations in renal expression patterns of Slc26a1 (SAT1) mRNA or protein. Urol Res 40:647–654. doi:10.1007/s00240-012-0480-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Geertsma ER, Chang YN, Shaik FR, Neldner Y, Pardon E, Steyaert J, Dutzler R (2015) Structure of a prokaryotic fumarate transporter reveals the architecture of the SLC26 family. Nat Struct Mol Biol 22:803–808. doi:10.1038/nsmb.3091

    Article  CAS  PubMed  Google Scholar 

  24. Glatt H, Meinl W (2004) Pharmacogenetics of soluble sulfotransferases (SULTs). Naunyn Schmiedeberg’s Arch Pharmacol 369:55–68. doi:10.1007/s00210-003-0826-0

    Article  CAS  Google Scholar 

  25. Good NE, Winget GD, Winter W, Connolly TN, Izawa S, Singh RM (1966) Hydrogen ion buffers for biological research. Biochemistry 5:467–477

    Article  CAS  PubMed  Google Scholar 

  26. Gorbunov D, Sturlese M, Nies F, Kluge M, Bellanda M, Battistutta R, Oliver D (2014) Molecular architecture and the structural basis for anion interaction in prestin and SLC26 transporters. Nat Commun 5:3622. doi:10.1038/ncomms4622

    Article  PubMed  PubMed Central  Google Scholar 

  27. Habuchi H, Habuchi O, Kimata K (2004) Sulfation pattern in glycosaminoglycan: does it have a code? Glycoconj J 21:47–52. doi:10.1023/B:GLYC.0000043747.87325.5e

    Article  CAS  PubMed  Google Scholar 

  28. Haila S, Hastbacka J, Bohling T, Karjalainen-Lindsberg ML, Kere J, Saarialho-Kere U (2001) SLC26A2 (diastrophic dysplasia sulfate transporter) is expressed in developing and mature cartilage but also in other tissues and cell types. J Histochem Cytochem Off J Histochem Soc 49:973–982

    Article  CAS  Google Scholar 

  29. Hassan HA, Mentone S, Karniski LP, Rajendran VM, Aronson PS (2007) Regulation of anion exchanger Slc26a6 by protein kinase C. Am J Physiol Cell Physiol 292:C1485–1492. doi:10.1152/ajpcell.00447.2006

    Article  CAS  PubMed  Google Scholar 

  30. Heneghan JF, Akhavein A, Salas MJ, Shmukler BE, Karniski LP, Vandorpe DH, Alper SL (2010) Regulated transport of sulfate and oxalate by SLC26A2/DTDST. Am J Physiol Cell Physiol 298:C1363–1375. doi:10.1152/ajpcell.00004.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hierholzer K, Cade R, Gurd R, Kessler R, Pitts R (1960) Stop-flow analysis of renal reabsorption and excretion of sulfate in the dog. Am J Phys 198:833–837

    CAS  Google Scholar 

  32. Jia C, Luo L, Kurogi K, Yu J, Zhou C, Liu MC (2015) Identification of the human SULT enzymes involved in the metabolism of rotigotine. J Clin Pharmacol. doi:10.1002/jcph.658

    PubMed  Google Scholar 

  33. Jiang Z, Asplin JR, Evan AP, Rajendran VM, Velazquez H, Nottoli TP, Binder HJ, Aronson PS (2006) Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6. Nat Genet 38:474–478. doi:10.1038/ng1762

    Article  CAS  PubMed  Google Scholar 

  34. Jun I, Cheng MH, Sim E, Jung J, Suh BL, Kim Y, Son H, Park K, Kim CH, Yoon JH, Whitcomb DC, Bahar I, Lee MG (2015) Pore dilation increases the bicarbonate permeability of CFTR, ANO1, and glycine receptor anion channels. J Physiol. doi:10.1113/jp271311

    Google Scholar 

  35. Karinou E, Compton EL, Morel M, Javelle A (2013) The Escherichia coli SLC26 homologue YchM (DauA) is a C(4)-dicarboxylic acid transporter. Mol Microbiol 87:623–640. doi:10.1111/mmi.12120

    Article  CAS  PubMed  Google Scholar 

  36. Karniski LP, Lotscher M, Fucentese M, Hilfiker H, Biber J, Murer H (1998) Immunolocalization of sat-1 sulfate/oxalate/bicarbonate anion exchanger in the rat kidney. Am J Phys 275:F79–87

    CAS  Google Scholar 

  37. Knight TF, Sansom SC, Senekjian HO, Weinman EJ (1981) Oxalate secretion in the rat proximal tubule. Am J Phys 240:F295–298

    CAS  Google Scholar 

  38. Ko N, Knauf F, Jiang Z, Markovich D, Aronson PS (2012) Sat1 is dispensable for active oxalate secretion in mouse duodenum. Am J Physiol Cell Physiol 303:C52–57. doi:10.1152/ajpcell.00385.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Krick W, Schnedler N, Burckhardt G, Burckhardt BC (2009) Ability of sat-1 to transport sulfate, bicarbonate, or oxalate under physiological conditions. Am J Physiol Cell Physiol 297:F145–154. doi:10.1152/ajprenal.90401.2008

    Article  CAS  Google Scholar 

  40. Kuo SM, Aronson PS (1988) Oxalate transport via the sulfate/HCO3 exchanger in rabbit renal basolateral membrane vesicles. J Biol Chem 263:9710–9717

    CAS  PubMed  Google Scholar 

  41. Lee A, Beck L, Markovich D (2003) The mouse sulfate anion transporter gene Sat1 (Slc26a1): cloning, tissue distribution, gene structure, functional characterization, and transcriptional regulation thyroid hormone. DNA Cell Biol 22:19–31. doi:10.1089/104454903321112460

    Article  CAS  PubMed  Google Scholar 

  42. Levitt MD, Furne J, Springfield J, Suarez F, DeMaster E (1999) Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa. J Clin Invest 104:1107–1114. doi:10.1172/jci7712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Li J, Xia F, Reithmeier RA (2014) N-glycosylation and topology of the human SLC26 family of anion transport membrane proteins. Am J Physiol Cell Physiol 306:C943–960. doi:10.1152/ajpcell.00030.2014

    Article  CAS  PubMed  Google Scholar 

  44. Liu XZ, Ouyang XM, Xia XJ, Zheng J, Pandya A, Li F, Du LL, Welch KO, Petit C, Smith RJH, Webb BT, Yan D, Arnos KS, Corey D, Dallos P, Nance WE, Chen ZY (2003) Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss. Hum Mol Genet 12:1155–1162. doi:10.1093/hmg/ddg127

    Article  CAS  PubMed  Google Scholar 

  45. Loriol C, Dulong S, Avella M, Gabillat N, Boulukos K, Borgese F, Ehrenfeld J (2008) Characterization of SLC26A9, facilitation of Cl(−) transport by bicarbonate. Cell Physiol Biochem Int J Exp Cell Physiol, Biochem Pharmacol 22:15–30. doi:10.1159/000149780

    Article  CAS  Google Scholar 

  46. Magen D, Berger L, Coady MJ, Ilivitzki A, Militianu D, Tieder M, Selig S, Lapointe JY, Zelikovic I, Skorecki K (2010) A loss-of-function mutation in NaPi-IIa and renal Fanconi’s syndrome. N Engl J Med 362:1102–1109. doi:10.1056/NEJMoa0905647

    Article  CAS  PubMed  Google Scholar 

  47. Markovich D (2011) Physiological roles of renal anion transporters NaS1 and Sat1. Am J Physiol Renal Physiol 300:F1267–1270. doi:10.1152/ajprenal.00061.2011

    Article  CAS  PubMed  Google Scholar 

  48. Markovich D (2012) Slc13a1 and Slc26a1 KO models reveal physiological roles of anion transporters. Physiology (Bethesda, Md) 27:7–14. doi:10.1152/physiol.00041.2011

    Article  CAS  Google Scholar 

  49. Morris ME, Levy G (1983) Serum concentration and renal excretion by normal adults of inorganic sulfate after acetaminophen, ascorbic acid, or sodium sulfate. Clin Pharmacol Ther 33:529–536

    Article  CAS  PubMed  Google Scholar 

  50. Nakada T, Zandi-Nejad K, Kurita Y, Kudo H, Broumand V, Kwon CY, Mercado A, Mount DB, Hirose S (2005) Roles of Slc13a1 and Slc26a1 sulfate transporters of eel kidney in sulfate homeostasis and osmoregulation in freshwater. Am J Physiol Regul, Integr Comp Physiol 289:R575–r585. doi:10.1152/ajpregu.00725.2004

    Article  CAS  Google Scholar 

  51. Nakanishi T, Otaki Y, Hasuike Y, Nanami M, Itahana R, Miyagawa K, Nishikage H, Izumi M, Takamitsu Y (2002) Association of hyperhomocysteinemia with plasma sulfate and urine sulfate excretion in patients with progressive renal disease. Am J Kidney Dis Off J Natl Kidney Found 40:909–915. doi:10.1053/ajkd.2002.36320

    Article  CAS  Google Scholar 

  52. Nazzal L, Puri S, Goldfarb DS (2015) Enteric hyperoxaluria: an important cause of end-stage kidney disease. Nephrol, Dial, Transplant Off Publ Eur Dial Transplant Assoc Eur Renal Assoc. doi:10.1093/ndt/gfv005

    Google Scholar 

  53. Nigwekar SU, Brunelli SM, Meade D, Wang W, Hymes J, Lacson E Jr (2013) Sodium thiosulfate therapy for calcific uremic arteriolopathy. Clin J Am Soc Nephrol 8:1162–1170. doi:10.2215/cjn.09880912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ohana E, Shcheynikov N, Park M, Muallem S (2012) Solute carrier family 26 member a2 (Slc26a2) protein functions as an electroneutral SOFormula/OH−/Cl− exchanger regulated by extracellular Cl. J Biol Chem 287:5122–5132. doi:10.1074/jbc.M111.297192

    Article  CAS  PubMed  Google Scholar 

  55. Ohana E, Yang D, Shcheynikov N, Muallem S (2009) Diverse transport modes by the solute carrier 26 family of anion transporters. J Physiol 587:2179–2185. doi:10.1113/jphysiol.2008.164863

    Article  CAS  PubMed  Google Scholar 

  56. Okonkwo OW, Batwara R, Granja I, Asplin JR, Goldfarb DS (2013) 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. PLoS One 8, e60380. doi:10.1371/journal.pone.0060380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Park HW, Nam JH, Kim JY, Namkung W, Yoon JS, Lee JS, Kim KS, Venglovecz V, Gray MA, Kim KH, Lee MG (2010) Dynamic regulation of CFTR bicarbonate permeability by [Cl−]i and its role in pancreatic bicarbonate secretion. Gastroenterology 139:620–631. doi:10.1053/j.gastro.2010.04.004

    Article  CAS  PubMed  Google Scholar 

  58. Planelles G (2004) Chloride transport in the renal proximal tubule. Pflugers Arch - Eur J Physiol 448:561–570. doi:10.1007/s00424-004-1309-y

    Article  CAS  Google Scholar 

  59. Quondamatteo F, Krick W, Hagos Y, Kruger MH, Neubauer-Saile K, Herken R, Ramadori G, Burckhardt G, Burckhardt BC (2006) Localization of the sulfate/anion exchanger in the rat liver. Am J Physiol Gastrointest Liver Physiol 290:G1075–1081. doi:10.1152/ajpgi.00492.2005

    Article  CAS  PubMed  Google Scholar 

  60. Regeer RR, Lee A, Markovich D (2003) Characterization of the human sulfate anion transporter (hsat-1) protein and gene (SAT1; SLC26A1). DNA Cell Biol 22:107–117. doi:10.1089/104454903321515913

    Article  CAS  PubMed  Google Scholar 

  61. Regeer RR, Markovich D (2004) A dileucine motif targets the sulfate anion transporter sat-1 to the basolateral membrane in renal cell lines. Am J Physiol Cell Physiol 287:C365–372. doi:10.1152/ajpcell.00502.2003

    Article  CAS  PubMed  Google Scholar 

  62. Reimold FR, Balasubramanian S, Doroquez DB, Shmukler BE, Zsengeller ZK, Saslowsky D, Thiagarajah JR, Stillman IE, Lencer WI, Wu BL, Villalpando-Carrion S, Alper SL (2015) Congenital chloride-losing diarrhea in a Mexican child with the novel homozygous SLC26A3 mutation G393W. Front Physiol 6:179. doi:10.3389/fphys.2015.00179

    Article  PubMed  PubMed Central  Google Scholar 

  63. Reimold FR, Heneghan JF, Stewart AK, Zelikovic I, Vandorpe DH, Shmukler BE, Alper SL (2011) Pendrin function and regulation in Xenopus oocytes. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol 28:435–450. doi:10.1159/000335106

    Article  CAS  Google Scholar 

  64. Romero MF, Chang MH, Plata C, Zandi-Nejad K, Mercado A, Broumand V, Sussman CR, Mount DB (2006) Physiology of electrogenic SLC26 paralogs. In: Epithelial anion transport in health and disease: the role of the SLC26 transport family. Novartis Foundation Symposium 273:126–147

  65. Romero MF, Chang MH, Plata C, Zandi-Nejad K, Mercado A, Broumand V, Sussman CR, Mount DB (2006) Physiology of electrogenic SLC26 paralogues. Novartis Found Symp 273:126–138, discussion 138–147, 261–124

    Article  CAS  PubMed  Google Scholar 

  66. Rungta RL, Choi HB, Tyson JR, Malik A, Dissing-Olesen L, Lin PJ, Cain SM, Cullis PR, Snutch TP, MacVicar BA (2015) The cellular mechanisms of neuronal swelling underlying cytotoxic edema. Cell 161:610–621. doi:10.1016/j.cell.2015.03.029

    Article  CAS  PubMed  Google Scholar 

  67. Salomon JJ, Spahn S, Wang X, Fullekrug J, Bertrand CA, Mall MA (2016) Generation and functional characterization of epithelial cells with stable expression of SLC26A9 Cl− channels. Am J Physiol Lung Cell Mol Physiol 00321:02015. doi:10.1152/ajplung.00321.2015

    Google Scholar 

  68. Santer R, Calado J (2010) Familial renal glucosuria and SGLT2: from a mendelian trait to a therapeutic target. Clin J Am Soc Nephrol 5:133–141. doi:10.2215/cjn.04010609

    Article  CAS  PubMed  Google Scholar 

  69. Satoh H, Susaki M, Shukunami C, Iyama K, Negoro T, Hiraki Y (1998) Functional analysis of diastrophic dysplasia sulfate transporter. Its involvement in growth regulation of chondrocytes mediated by sulfated proteoglycans. J Biol Chem 273:12307–12315

    Article  CAS  PubMed  Google Scholar 

  70. Schnedler N, Burckhardt G, Burckhardt BC (2011) Glyoxylate is a substrate of the sulfate-oxalate exchanger, sat-1, and increases its expression in HepG2 cells. J Hepatol 54:513–520. doi:10.1016/j.jhep.2010.07.036

    Article  CAS  PubMed  Google Scholar 

  71. Senekjian HO, Weinman EJ (1982) Oxalate transport by proximal tubule of the rabbit kidney. Am J Phys 243:F271–275

    CAS  Google Scholar 

  72. Shcheynikov N, Kim KH, Kim KM, Dorwart MR, Ko SB, Goto H, Naruse S, Thomas PJ, Muallem S (2004) Dynamic control of cystic fibrosis transmembrane conductance regulator Cl(−)/HCO3(−) selectivity by external Cl(−). J Biol Chem 279:21857–21865. doi:10.1074/jbc.M313323200

    Article  CAS  PubMed  Google Scholar 

  73. Shcheynikov N, Son A, Hong JH, Yamazaki O, Ohana E, Kurtz I, Shin DM, Muallem S (2015) Intracellular Cl− as a signaling ion that potently regulates Na+/HCO3− transporters. Proc Natl Acad Sci U S A 112:E329–337. doi:10.1073/pnas.1415673112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Srinivasan L, Baars TL, Fendler K, Michel H (2016) Functional characterization of solute carrier (SLC) 26/sulfate permease (SulP) proteins in membrane mimetic systems. Biochim Biophys Acta 1858:698–705. doi:10.1016/j.bbamem.2016.01.006

    Article  CAS  PubMed  Google Scholar 

  75. Stewart AK, Chernova MN, Kunes YZ, Alper SL (2001) Regulation of AE2 anion exchanger by intracellular pH: critical regions of the NH(2)-terminal cytoplasmic domain. Am J Physiol Cell Physiol 281:C1344–1354

    CAS  PubMed  Google Scholar 

  76. Subramanian VS, Nabokina SM, Patton JR, Marchant JS, Moradi H, Said HM (2013) Glyoxalate reductase/hydroxypyruvate reductase interacts with the sodium-dependent vitamin C transporter-1 to regulate cellular vitamin C homeostasis. Am J Physiol Gastrointest Liver Physiol 304:G1079–1086. doi:10.1152/ajpgi.00090.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Sun L, Rommens JM, Corvol H, Li W, Li X, Chiang TA, Lin F, Dorfman R, Busson PF, Parekh RV, Zelenika D, Blackman SM, Corey M, Doshi VK, Henderson L, Naughton KM, O’Neal WK, Pace RG, Stonebraker JR, Wood SD, Wright FA, Zielenski J, Clement A, Drumm ML, Boelle PY, Cutting GR, Knowles MR, Durie PR, Strug LJ (2012) Multiple apical plasma membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis. Nat Genet 44:562–569. doi:10.1038/ng.2221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Wang X, Yang S, Jia S, He DZ (2010) Prestin forms oligomer with four mechanically independent subunits. Brain Res 1333:28–35. doi:10.1016/j.brainres.2010.03.070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Wangemann P (2013) Mouse models for pendrin-associated loss of cochlear and vestibular function. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol 32:157–165. doi:10.1159/000356635

    Article  CAS  Google Scholar 

  80. Wedenoja S, Pekansaari E, Hoglund P, Makela S, Holmberg C, Kere J (2011) Update on SLC26A3 mutations in congenital chloride diarrhea. Hum Mutat 32:715–722. doi:10.1002/humu.21498

    Article  CAS  PubMed  Google Scholar 

  81. Weinstein AM, Weinbaum S, Duan Y, Du Z, Yan Q, Wang T (2007) Flow-dependent transport in a mathematical model of rat proximal tubule. Am J Physiol Renal Physiol 292:F1164–1181. doi:10.1152/ajprenal.00392.2006

    Article  CAS  PubMed  Google Scholar 

  82. Xie Q, Welch R, Mercado A, Romero MF, Mount DB (2002) Molecular characterization of the murine Slc26a6 anion exchanger: functional comparison with Slc26a1. Am J Physiol Renal Physiol 283:F826–838. doi:10.1152/ajprenal.00079.2002

    Article  PubMed  Google Scholar 

  83. Xu J, Song P, Miller ML, Borgese F, Barone S, Riederer B, Wang Z, Alper SL, Forte JG, Shull GE, Ehrenfeld J, Seidler U, Soleimani M (2008) Deletion of the chloride transporter Slc26a9 causes loss of tubulovesicles in parietal cells and impairs acid secretion in the stomach. Proc Natl Acad Sci U S A 105:17955–17960. doi:10.1073/pnas.0800616105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Xu J, Song P, Nakamura S, Miller M, Barone S, Alper SL, Riederer B, Bonhagen J, Arend LJ, Amlal H, Seidler U, Soleimani M (2009) Deletion of the chloride transporter slc26a7 causes distal renal tubular acidosis and impairs gastric acid secretion. J Biol Chem 284:29470–29479. doi:10.1074/jbc.M109.044396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Yin K, Lei Y, Wen X, Lacruz RS, Soleimani M, Kurtz I, Snead ML, White SN, Paine ML (2015) SLC26A gene family participate in pH regulation during enamel maturation. PLoS One 10, e0144703. doi:10.1371/journal.pone.0144703

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

The authors thank Norma Guerra, MD (Hospital IMSS la Raza, Ciudad de Mexico, Mexico) for patient samples.

Author information

Authors and Affiliations

  1. Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433, China

    Meng Wu & Bai-Lin Wu

  2. Division of Laboratory Medicine, Boston Children’s Hospital, Boston, MA, 02115, USA

    Meng Wu & Bai-Lin Wu

  3. Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA

    Meng Wu, John F. Heneghan, David H. Vandorpe & Seth L. Alper

  4. Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA

    John F. Heneghan, David H. Vandorpe & Seth L. Alper

  5. Department of Physiology, Faculty of Medicine, Universidad Nacional Autonoma de Mexico, Mexico, DF, 04510, Mexico

    Laura I. Escobar

  6. Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA

    Seth L. Alper

Authors
  1. Meng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John F. Heneghan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David H. Vandorpe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Laura I. Escobar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bai-Lin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Seth L. Alper
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seth L. Alper.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Fig. S1

SLC26A1 mediates electroneutral SO4 2− uptake. Oocytes previously uninjected (a, c) or injected with 5 ng cRNA encoding SLC26A1 (b, d) were subjected to two-electrode voltage clamp measurements. Currents were recorded at the indicated clamp potentials during sequential exposure to baths of ND96(cyclamate), then of ND96(cyclamate) with added 5 mM SO4 2−, and finally of ND96(cyclamate) containing 5 mM SO4 2− plus 100 M DIDS (a, b). Alternatively, currents were recorded during sequential exposure to baths of ND96(cyclamate) followed by ND64(sulfate) (c, d). (PDF 75 kb)

Fig. S2

Effects of sulfonate (“Good”) buffers on SLC26A1. SLC26A1-mediated SO4 2− uptake (5 ng cRNA) from baths containing 1 mM SO4 2− in ND96(Cl−) (104 mM Cl− plus 5 mM HEPES) or in baths containing 69 mM Cl− plus 40 mM of the indicated buffers. SO4 2− uptake by uninjected oocytes was in ND96(Cl−) containing 1 mM SO4 2− (mean ± SE for (n) oocytes). (PDF 50 kb)

Fig. S3

Effects of extracellular Ca2+ and Mg2+ on SLC26A1. SLC26A1-mediated SO4 2− uptake (5 ng cRNA) from baths containing 1 mM SO4 2− in either ND96(Cl−), ND96(gluconate), or their nominally Ca2+- and Mg2+-free versions, as indicated (mean ± SE, n = 10). (PDF 32 kb)

Fig. S4

pHo regulates SLC26A1-associated Cl- flux independent of order of pHo exposure. a) 36Cl- efflux traces from representative individual oocytes previously uninjected (triangles) or injected with 40 ng SLC26A1 cRNA (circles) during sequential exposure to ND96(Cl-) bath first at pH 8.5, then at pH 5.0, with subsequent addition of 200 M DIDS. Note that this order of pH exposure is reversed from that shown in Fig 7b,d. b) Mean 36Cl- efflux rate constants (± SE for (n) oocytes) from experiments as in panel a (***, p < 0.001). (PDF 51 kb)

Fig. S5

Effects of cAMP and Ca2+ on SLC26A1. a SLC26A1-expressing oocytes (5 ng cRNA) were pre-incubated 30 min in baths of ND96(Cl−) or ND96(gluconate) in the absence or presence of 1 mM dibutyryl cAMP (db-cAMP) and/or 0.5 mM Isobutylmethylxanthine (IBMX), followed by a 30-min uptake assay in the same baths supplemented by 1 mM SO4 2−. b SLC26A1-expressing oocytes (5 ng cRNA) were pre-incubated 4 h in ND96(Cl−) or ND96(gluconate) containing 100 μM BAPTA-AM or 0.2 % DMSO (vehicle), then subjected to 30 min SO4 2− uptake assays in the same baths supplemented by 1 mM SO4 2−. Additional SLC26A1-expressing oocytes were injected with 50 nl disodium EGTA (50 mM, pH 7.4) or NaCl (50 mM), incubated 30 min in ND96(Cl−) or ND96(gluconate), and subjected to 30 min SO4 2− uptake assays in the same baths supplemented by 1 mM SO4 2− (mean ± SE, n = 10). (PDF 124 kb)

Table S1

(PDF 87 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, M., Heneghan, J.F., Vandorpe, D.H. et al. Extracellular Cl− regulates human SO4 2−/anion exchanger SLC26A1 by altering pH sensitivity of anion transport. Pflugers Arch - Eur J Physiol 468, 1311–1332 (2016). https://doi.org/10.1007/s00424-016-1823-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-016-1823-8

Keywords

Search

Navigation