Expression, Regulation and the Role of SLC26 Cl − /HCO 3 − Exchangers in Kidney and Gastrointestinal Tract

Abstract

SLC26 isoforms are members of a large, conserved family of anion exchangers that display highly restricted and distinct tissue distribution. Cloning experiments have identified the existence of 10 SLC26 genes or isoforms (SLC26A1-11). The products of all, excepting SLC26A5 (prestin), function as anion exchangers with versatility with respect to transported anions. Modes of transport mediated by SLC26 members include the exchange of chloride for bicarbonate, hydroxyl, sulfate, formate, iodide, or oxalate with variable specificity. Several members of SLC26 family mediate chloride-bicarbonate exchange and display expression in a limited number of tissues including the gastrointestinal tract and/or kidney, with distinct subcellular (apical or basolateral) localization. These include SLC26A3 (DRA), SLC26A4 (pendrin), SLC26A6 (PAT1 or CFEX), SLC26A7 and SLC26A9. SLC26A3 and A9 are not expressed in the kidney but SLC26A4, A6 and A7 are. Genetically engineered null mice have highlighted the important role of two members of the SLC26 family, SLC26A4 and SLC26A6, in homeostatic function in kidney and/or intestine. In conjunction with expression studies, the evolving picture points to important roles for SLC26 family in chloride, bicarbonate, oxalate or sulfate transport and homeostasis in gastrointestinal tract, kidney and several other tissues. This review in particular focuses on the role and regulation of SLC26A6, A7 and A9 in the kidney and/or gastrointestinal tract.