PDZ-domain interactions and apical expression of type IIa Na/Pi cotransporters

Nati Hernando, Nadine Déliot, Serge M. Gisler, Eleanor Lederer, Edward J. Weinman, Jürg Biber, Heini Murer

Research output: Contribution to journalArticlepeer-review

151 Scopus citations

Abstract

Type IIa Na/Pi cotransporters are expressed in renal proximal brush border and are the major determinants of inorganic phosphate (Pi) reabsorption. Their carboxyl-terminal tail contains information for apical expression, and interacts by means of its three terminal amino acids with several PSD95/DglA/ZO-1-like domain (PDZ)-containing proteins. Two of these proteins, NaPi-Cap1 and Na/H exchanger-regulatory factor 1 (NHERF1), colocalize with the co-transporter in the proximal brush border. We used opossum kidney cells to test the hypothesis of a potential role of PDZ-interactions on the apical expression of the cotransporter. We found that opossum kidney cells contain NaPi-Cap1 and NHERF1 mRNAs. For NHERF1, an apical location of the protein could be documented; this location probably reflects interaction with the cytoskeleton by means of the MERM-binding domain. Overexpression of PDZ domains involved in interaction with the cotransporter (PDZ-1/NHERF1 and PDZ-3/NaPi-Cap1) had a dominant-negative effect, disturbing the apical expression of the cotransporter without affecting the actin cytoskeleton or the basolateral expression of Na/K-ATPase. These data suggest an involvement of PDZ-interactions on the apical expression of type IIa cotransporters.

Original languageEnglish (US)
Pages (from-to)11957-11962
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number18
DOIs
StatePublished - Sep 3 2002
Externally publishedYes

Keywords

  • Na/H exchanger-regulatory factor 1
  • Opossum kidney cells
  • Proximal tubules

ASJC Scopus subject areas

  • General

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