無機リン酸トランスポーターの細胞膜局在制御機構

抄録

Phosphate (Pi) homeostasis is mainly regulated by control of Pi reabsorption in the kidney. Sodium-dependent Pi transport system localized in brush border membrane of renal tubular cells is a responsible for the Pi reabsorption. Until now, three isoform of the sodium-dependent phosphate transporter (NaPi-I, NaPi-IIa, NaPi-IIc) have been identified in the brush border membrane of the renal proximal tubular cells. Among them, NaPi-IIa is the most regulatable transporter by various hormone and environmental changes. PTH is a potent inhibitor of NaPi-IIa and is rapidly involved in the translocation of NaPi-IIa from plasma membrane to intracellular compartments. Recent studies demonstrated that NaPi-IIa can predominantly localize in the membrane microdomains (such as lipid rafts or caveolae) of apical membrane of renal proximal tubular cells, and NaPi-IIa can bind to actin cytoskeleton via NHERF-1/EBP50 and ezrin. Formation of the complex has thought to be important to determine the subcellular localization and hormonal regulation of the NaPi-IIa. We identified ezrin is a target molecule for PTH signal. Repression of ezrin function inhibited both membrane targeting and PTH-dependent endocytosis of NaPi-IIa. These findings suggest that ezrin would be a key molecule for both subcellular localization and hormonal regulation of the NaPi-IIa. [J Physiol Sci. 2006;56 Suppl:S10]