Solute carrier family 26 member 6 (SLC26A6) (SLC26A6)

Solute carrier family 26 member 6 (SLC26A6), also known as PAT-1, is a transmembrane protein that functions as an anion exchanger on the apical membrane of epithelial cells, particularly in the intestine, kidney, and pancreas. Its primary biological function in the colon is to facilitate the secretion of oxalate from the blood into the intestinal lumen in exchange for chloride or bicarbonate, thereby playing a critical role in systemic oxalate homeostasis. This transport process is dynamically regulated by the Protein Kinase A (PKA) signaling pathway, which increases the surface expression and intrinsic activity of both SLC26A6 and its related family member, SLC26A2. Dysregulation or deficiency of this pathway is linked to hyperoxaluria, a condition characterized by high levels of oxalate in the urine, which is a major risk factor for the development of calcium oxalate kidney stones (nephrolithiasis) and chronic kidney disease. Therapeutic strategies targeting this system involve the use of secretagogues, such as the Oxalobacter formigenes-derived peptides P8 and P9, which activate the PKA pathway to enhance enteric oxalate secretion. By leveraging the intestine as an extra-renal route for oxalate elimination, these drugs aim to reduce plasma and urinary oxalate levels, providing a novel treatment for primary and secondary hyperoxaluria. While promising, therapeutic challenges include ensuring gut-restricted activity to avoid systemic side effects of PKA activation and maintaining the balance of other anions like sulfate and chloride.

Other names

PAT-1Putative anion transporter 1SLC26A6Solute carrier family 26 member 2 (SLC26A2)DTDSTDiastrophic dysplasia sulfate transporterOxalate transporter

Activation of the Protein Kinase A (PKA) signaling pathway leads to the phosphorylation and increased apical membrane trafficking of SLC26A6 and SLC26A2, thereby enhancing transcellular oxalate secretion from the blood into the intestinal lumen.