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Expression and regulation of the renal Na/phosphate cotransporter NaPi-IIa in a mouse model deficient for the PDZ protein PDZK1.

Authors :
Capuano, Paola
Bacic, Desa
Stange, Gerti
Hernando, Nati
Kaissling, Brigitte
Pal, Rinku
Kocher, Olivier
Biber, Jürg
Wagner, Carsten
Murer, Heini
Source :
Pflügers Archiv: European Journal of Physiology; Jan2005, Vol. 449 Issue 4, p392-402, 11p
Publication Year :
2005

Abstract

Inorganic phosphate (P<subscript>i</subscript>) is reabsorbed in the renal proximal tubule mainly via the type-IIa sodium-phosphate cotransporter (NaPi-IIa). This protein is regulated tightly by different factors, among them dietary P<subscript>i</subscript> intake and parathyroid hormone (PTH). A number of PDZ-domain-containing proteins have been shown to interact with NaPi-IIa in vitro, such as Na<superscript>+</superscript>/H<superscript>+</superscript> exchanger-3 regulatory factor-1 (NHERF1) and PDZK1. PDZK1 is highly abundant in kidney and co-localizes with NaPi-IIa in the brush border membrane of proximal tubules. Recently, a knock-out mouse model for PDZK1 (Pdzk1<superscript>-/-</superscript>) has been generated, allowing the role of PDZK1 in the expression and regulation of the NaPi-IIa cotransporter to be examined in in vivo and in ex vivo preparations. The localization of NaPi-IIa and other proteins interacting with PDZK1 in vitro [Na<superscript>+</superscript>/H<superscript>+</superscript> exchanger (NHE3), chloride-formate exchanger (CFEX)/putative anion transporter-1 (PAT1), NHERF1] was not altered inPdzk1<superscript>-/-</superscript> mice. The abundance of NaPi-IIa adapted to acute and chronic changes in dietary P<subscript>i</subscript> intake, but steady-state levels of NaPi-IIa were reduced inPdzk1<superscript>-/-</superscript> under a P<subscript>i</subscript> rich diet. This was paralleled by a higher urinary fractional P<subscript>i</subscript> excretion. The abundance of the anion exchanger CFEX/PAT1 (SLC26A6) was also reduced. In contrast, NHERF1 abundance increased in the brush border membrane ofPdzk1<superscript>-/-</superscript> mice fed a high-P<subscript>i</subscript> diet. Acute regulation of NaPi-IIa by PTH in vivo and by PTH and activators of protein kinases A, C and G (PKA, PKC and PKG) in vitro (kidney slice preparation) was not altered inPdzk1<superscript>-/-</superscript> mice. In conclusion, loss of PDZK1 did not result in major changes in proximal tubule function or NaPi-IIa regulation. However, under a P<subscript>i</subscript>-rich diet, loss of PDZK1 reduced NaPi-IIa abundance indicating that PDZK1 may play a role in the trafficking or stability of NaPi-IIa under these conditions. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00316768
Volume :
449
Issue :
4
Database :
Complementary Index
Journal :
Pflügers Archiv: European Journal of Physiology
Publication Type :
Academic Journal
Accession number :
16243931
Full Text :
https://doi.org/10.1007/s00424-004-1351-9