A ‘complexity’ of urate transporters

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Presentation transcript:

A ‘complexity’ of urate transporters Alan F. Wright, Igor Rudan, Nicholas D. Hastie, Harry Campbell Kidney International Volume 78, Issue 5, Pages 446-452 (September 2010) DOI: 10.1038/ki.2010.206 Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 1 Model of urate transport in the proximal convoluted tubules (PCT) of the kidney. Proteins influencing urate transport in the kidney identified by recent genome-wide association studies (GWAS)23 are shown in red and others are shown in green. GLUT9 (isoform 1) is thought to be the major basolateral urate transporter in renal tubular cells contributing to the reabsorption of urate into the blood and interstitial fluid. The apical URAT1 transporter is proposed to exchange urate anion for organic anions such as lactate and is functionally coupled to sodium monocarboxylate cotransporters (SMCT1, SMCT2) that transport lactate into the cell driven by an inward sodium gradient.49 The PDZK1 scaffold protein is thought to bind urate transporters such as URAT1, OAT4, and NPT1, and may form a bidirectional transport system (transportosome) that can functionally couple different transporters. The role of GLUT9ΔN (isoform 2) on apical PCT membranes is unclear but has been proposed to exchange luminal glucose for intracellular urate15 although the data of Dinour et al.43 argue against this. It may mediate urate entry into PCT cells indirectly coupled to the export of an as yet unidentified anion. Other proteins concerned with the apical reabsorption of urate include the organic anion exchanger OAT4 (SLC22A11). Proteins mediating urate secretion into urine by PCT cells have also been clarified by recent GWAS (see text). These are proposed to include the apical PCT transporters ABCG2, NPT1, and NPT4, whereas other evidence supports a role for MRP4 and UAT/galectin-9, which may constitutively excrete urate produced by intracellular metabolism. Kidney International 2010 78, 446-452DOI: (10.1038/ki.2010.206) Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 2 Principles underlying Mendelian randomization as a means of causal inference to dissect the role of uric acid in human disease. Kidney International 2010 78, 446-452DOI: (10.1038/ki.2010.206) Copyright © 2010 International Society of Nephrology Terms and Conditions