PDZタンパク質による有機アニオントランスポーターの制御

抄録

Organic Anion Transporters (OATs), belonging to SLC22 family, are mainly localized in the renal proximal tubules and play important roles in the detoxification and the secretion of xenobiotics such as drugs and toxins and in the reabsorption of endogenous organic anions such as urate and estrone sulfate. Recently, it has been reported that the transporters at the apical membrane of the proximal tubules that have PDZ motif at their extreme C-terminus bind to the NHERF family proteins via PDZ interaction. They exist and function on the network consisted of such proteins beneath the plasma membrane (Anzai et al., Curr Opin Nephrol Hypertens, 2005). Our yeast two-hybrid assays revealed that urate transporter URAT1 and organic anion transporter OAT4, localized at the apical membrane of the proximal tubules, interact with PDZ proteins. The interaction of PDZ proteins enhanced their transport activity in the overexpressed mammalian cells through the increased surface protein expression (Anzai et al., J Biol Chem, 2004: Miyazaki et al., J Am Soc Nephrol, 2005). To date, other transporters related to the renal organic anion handling have also been found to interact with PDZ proteins. These results indicate that the organic anion transport molecular complex (organic anion transportsome) is formed through apical PDZ network and it may contribute to the renal organic anion handling as a functional unit. [J Physiol Sci. 2006;56 Suppl:S9]