Solute Carrier Family 26 Member a2 (Slc26a2) Protein Functions as an Electroneutral SO42-/OH-/Cl- Exchanger Regulated by Extracellular Cl-

Ehud Ohana, Nikolay Shcheynikov, Meeyoung Park, Shmuel Muallem

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Slc26a2 is a ubiquitously expressed SO42− transporter with high expression levels in cartilage and several epithelia. Mutations in SLC26A2 are associated with diastrophic dysplasia. The mechanism by which Slc26a2 transports SO42− and the ion gradients that mediate SO42− uptake are poorly understood. We report here that Slc26a2 functions as an SO42−/2OH−, SO42−/2Cl−, and SO42−/OH−/Cl− exchanger, depending on the Cl− and OH− gradients. At inward Cl− and outward pH gradients (high Cl−o and low pHo) Slc26a2 functions primarily as an SO42−o/2OH−i exchanger. At low Cl−o and high pHo Slc26a2 functions increasingly as an SO42−o/2Cl−i exchanger. The reverse is observed for SO42−i/2OH−o and SO42−i/2Cl−o exchange. Slc26a2 also exchanges Cl− for I−, Br−, and NO3− and Cl−o competes with SO42− on the transport site. Interestingly, Slc26a2 is regulated by an extracellular anion site, required to activate SO42−i/2OH−o exchange. Slc26a2 can transport oxalate in exchange for OH− and/or Cl− with properties similar to SO42− transport. Modeling of the Slc26a2 transmembrane domain (TMD) structure identified a conserved extracellular sequence 367GFXXP371 between TMD7 and TMD8 close to the conserved Glu417 in the permeation pathway. Mutation of Glu417 eliminated transport by Slc26a2, whereas mutation of Phe368 increased the affinity for SO42−o 8-fold while reducing the affinity for Cl−o 2 fold, but without affecting regulation by Cl−o. These findings clarify the mechanism of net SO42− transport and describe a novel regulation of Slc26a2 by an extracellular anion binding site and should help in further understanding aberrant SLC26A2 function in diastrophic dysplasia.

Original languageEnglish GB
Pages (from-to)5122-5132
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number7
DOIs
StatePublished - 10 Feb 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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