Specificity and Regulation of Renal Sulfate Transporters

Sulfate is essential for normal cellular function. The kidney plays a major role in sulfate homeostasis. Sulfate is freely filtered and then undergoes net reabsorption in the proximal tubule. The apical membrane Na⁺/sulfate cotransporter NaS1 (SLC13A1) has a major role in mediating proximal tubule sulfate reabsorption, as demonstrated by the findings of hyposulfatemia and hypersulfaturia in Nas1-null mice. The anion exchanger SAT1 (SLC26A1), the founding member of the SLC26 sulfate transporter family, mediates sulfate exit across the basolateral membrane to complete the process of transtubular sulfate reabsorption. Another member of this family, CFEX (SLC26A6), is present at the apical membrane of proximal tubular cells. It also can transport sulfate by anion exchange, which probably mediates backflux of sulfate into the lumen. Knockout mouse studies have demonstrated a major role of CFEX as an apical membrane Cl⁻/oxalate exchanger that contributes to NaCl reabsorption in the proximal tubule. Several additional SLC26 family members mediate sulfate transport and show some level of renal expression (e.g., SLC26A2, SLC26A7, SLC26A11). Their roles in mediating renal tubular sulfate transport are presently unknown. This paper reviews current data available on the function and regulation of three sulfate transporters (NaS1, SAT1, and CFEX) and their physiological roles in the kidney.