PDZ-domain interactions and apical expression of type IIa Na/P(i) cotransporters.
Type IIa Na/P(i) cotransporters are expressed in renal proximal brush border and are the major determinants of inorganic phosphate (P(i)) 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 cotransporter 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.
Hernando
Nati
N
Institute of Physiology, University of Zurich, Wintherthurerstrasse 190, CH-8057 Zurich, Switzerland.
Déliot
Nadine
N
Gisler
Serge M
SM
Lederer
Eleanor
E
Weinman
Edward J
EJ
Biber
Jürg
J
Murer
Heini
H
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D017923:Sodium-Hydrogen Exchangers; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters / Q000737:chemistry / Q000378:metabolism*
D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; C093376:sodium-hydrogen exchanger regulatory factor