Solute carrier family 2, member 9 and uric acid homeostasis

Abstract

The goal of this article is to review the possible physiological roles of the recently identified urate transporter, solute carrier family 2 (facilitated glucose transporter), member 9 (SLC2A9), in the renal handling of urate. Glucose transporter 9 is a high affinity hexose transporter encoded by the SLC2A9 gene found on human chromosome 4. The two splice variants SLC2A9b and SLC2A9a are expressed in the apical and basolateral membranes, respectively, of the proximal convoluted tubule. Recent reports have found significant correlations between two different sets of single nucleotide polymorphisms in SLC2A9. In one case, they are associated with increases in plasma urate levels and/or the incidence of hypertension or gout. The second set of single nucleotide polymorphisms correlate with hypouricaemia in Japanese patients. Expression of SLC2A9a and b in Xenopus laevis oocytes shows that these proteins mediate rapid urate fluxes and can exchange glucose for urate. Indirect evidence also suggests that the transporter is electrogenic. This review proposes that SLC2A9 contributes significantly in two ways to the fluxes of urate across the proximal convoluted tubule. Firstly, the apical expression of SLC2A9b secretes urate back into the urine in exchange for lumenal glucose. Secondly, the basolateral membrane SLC2A9a could be the primary route for urate movement out of the epithelium into the peritubular space.