STIMULATION OF RAT TYPE IIA SODIUM DEPENDENT PHOSPHATE COTRANSPORTER (NAPI-2) BY SERUM AND GLUCOCORTICOID-INDUCED KINASE SGK1 AND NA+/H+ EXCHANGE REGULATING FACTOR NHERF2

Hamdy M Embark

doi:10.21608/avmj.2015.170254

Abstract

Inorganic phosphate (Pi) is reabsorbed in the renal proximal convoluted tubules mainly via the electrogenic sodium dependent phosphate cotransporter NaPi Type IIa (NaPi-IIa). The isoforms of NaPi-IIa have been cloned from different species such as rat (NaPi-2). Serum and glucocorticoid-induced kinase 1 (SGK1) and rat sodium dependent phosphate cotransporter (NaPi-2) are highly expressed in the brush border membrane (BBM) of proximal tubule cells. The significance of the kinase in regulation of sodium dependent phosphate cotransporter (NaPi-2) has, however, remained elusive. On the other hand, the carboxyl-terminal tail of NaPi-2 contains information for apical expression, and interacts by means of its three terminal amino acids with several PSD95/DglA/ZO-1-like domains (PDZ)-containing proteins such as Na+/H+ exchanger 3 regulatory factors NHERF1 or NHERF2. Both, NHERF1 and NHERF2 modulate the targeting and trafficking of several proteins into the plasma membrane. Trafficking of the Na+/H+ exchanger NHE3 is controlled by NHE regulating factor NHERF2 and serum and glucocorticoid-inducible kinase SGK1. To test for a possible involvement in NaPi-2 regulation, cRNA encoding NaPi-2 was injected into Xenopuslaevis oocytes with or without additional injection of cRNA encoding SGK1 and/or NHERF2. Using two-electrode voltage-clamp, the transport activity was quantified as the substrate-induced current. Exposure to 1 mM phosphate induced an inward current (IP) in NaPi-2 expressing oocytes but not in water injected oocytes. Coexpression of SGK1 in NaPi-2 expressing oocytes significantly stimulated the phosphate-induced inward current. Moreover, coexpression of NHERF2 also significantly stimulated the phosphate-induced inward current in NaPi-2 expressing oocytes. The effect of SGK1 on NaPi-2 is mimicked by additional coexpression of NHERF2. The observations suggest that SGK1 and NHERF2 regulate NaPi-2 activity and are thus likely to participate in the stimulatory effect of some hormones, such as growth hormone and insulin, on renal phosphate transport. The present results thus disclose novel signaling mechanisms regulating NaPi-2 activity and renal phosphate transport, which may be important for regulation of phosphate homeostasis.

Highlights

Inorganic phosphate (Pi) is reabsorbed in the renal proximal convoluted tubules mainly via the electrogenic sodium dependent phosphate cotransporter NaPi Type IIa (NaPi-IIa)
The maintenance of Pi homeostasis is a critical event to the appropriate growth and well-being of both young and adult animals (Adedokun and Adeola, 2013), because it is necessary for the development, maintenance, and repair of bone and tissues components involved is sodium dependent phosphate cotransporter system localized in the brush border membrane of the tubular epithelium which mediates the uptake of Pi against the electrochemical gradient from primary urine into the cell (Forster et al, 1997)
(p < 0.05) higher phosphate induced inward currents were observed in oocytes injected with Serum and glucocorticoid-induced kinase 1 (SGK1) and NaPi-2 (7.4 ± 0.9 nA, n = 14) than the respective value in oocytes expressing NaPi-2 alone

Summary

Introduction

Inorganic phosphate (Pi) is reabsorbed in the renal proximal convoluted tubules mainly via the electrogenic sodium dependent phosphate cotransporter NaPi Type IIa (NaPi-IIa). Serum and glucocorticoid-induced kinase 1 (SGK1) and rat sodium dependent phosphate cotransporter (NaPi-2) are highly expressed in the brush border membrane (BBM) of proximal tubule cells. The maintenance of Pi homeostasis is a critical event to the appropriate growth and well-being of both young and adult animals (Adedokun and Adeola, 2013), because it is necessary for the development, maintenance, and repair of bone and tissues components involved is sodium dependent phosphate cotransporter system localized in the brush border membrane of the tubular epithelium which mediates the uptake of Pi against the electrochemical gradient from primary urine into the cell (Forster et al, 1997). Type I cotransporter (NaPi-1) induces an anion channel (Yanagawa et al, 1999), type IIa is the renal brush border sodium dependent phosphate cotransporter and type IIb is found apically in many tissues including the small intestine and the lung, but not the kidney (Murer et al, 2000). Type III cotransporters are being found every where including renal tubules (Werner and Kinne, 2001)

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Discussion

Conclusion