SLC26 chloride/base exchangers in the kidney in health and disease

Abstract

Solute-linked carrier 26 (SLC26) isoforms are members of a large, conserved family of anion exchangers, many of which display highly restricted and distinct tissue distribution. Cloning experiments have identified 10 SLC26 genes or isoforms (SLC26A1-11). Except for SLC26A5 (prestin), all 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. Other anion exchange modes not involving chloride also have been reported for some of the members of this family. Several members of SLC26 isoforms are expressed in the kidney. These include SLC26A1 (SAT1), SLC26A4 (pendrin), SLC26A6 (putative anion transporter [PAT1] or chloride/formate exchange [CFEX]), SLC26A7, and SLC26A11. Each isoform displays a specific nephron segment distribution with a distinct subcellular localization. Coupled to expression studies and examination of genetically engineered mice deficient in various SLC26 isoforms, the evolving picture points to important roles for the SLC26 family in chloride absorption, vascular volume homeostasis, acid-base regulation, and oxalate excretion in the kidney. This review summarizes recent advances in the identification and characterization of SLC26 family members, with specific emphasis on their distribution and role in kidney physiology. Specifically, the roles of A4 (pendrin), A6 (PAT1), and A7 (PAT2) in chloride homeostasis, oxalate excretion, and acid-base balance are discussed.