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- Title
PDZK1: I. A major scaffolder in brush borders of proximal tubular cells.
- Authors
Gisler, Serge M.; Pribanic, Sandra; Bacic, Desa; Forrer, Patrik; Gantenbein, Andrea; Sabourin, Luc A.; Tsuji, Akira; Zhuo-Shen Zhao, Akira; Manser, Edward; Biber, Jürg; Murer, Heini
- Abstract
PDZK1: I. A major scaffolder in brush borders of proximal tubular cells. In proximal tubular cells, PDZK1 (NaPi-Cap1) has been implicated in apical expression of the Na+-dependent phosphate cotransporter (NaPi-IIa) via interaction with its C-terminus. PDZK1 represents a multidomain protein consisting of four PDZ domains and thus is believed to have a broader specificity besides NaPi-IIa. We subjected single PDZ domains derived from PDZK1 either to yeast two-hybrid screens or yeast trap assays. Different pull-down assays and blot overlays were applied to corroborate the PDZK1-mediated interactions in vitro. Co-localization of interacting proteins with PDZK1 in proximal tubular cells was assessed by immunohistochemistry. In the yeast screens, the most abundant candidate protein to interact with PDZK1 was the membrane-associated protein of 17 kD (MAP17). Besides MAP17, C-terminal parts of following transporters were also identified: NaPi-IIa, solute carrier SLC17A1 (NaPi-I), Na+/H+ exchanger (NHE-3), organic cation transporter (OCTN1), chloride-formate exchanger (CFEX), and urate-anion exchanger (URAT1). In addition, other regulatory factors were found among the clones, such as a protein kinase A (PKA)-anchoring protein (D-AKAP2) and N+/H+ exchanger regulator factor (NHERF-1). All interactions of itemized proteins with PDZK1 were affirmed by in vitro techniques. Apart from PDZK1, strong in vitro interactions of NHERF-1 were also observed with the solute transporters (excluding MAP17) and D-AKAP2. All identified proteins were immunolocalized in proximal tubular cells, wherein all membrane proteins co-localized with PDZK1 in brush borders. We hypothesize that PDZK1 and NHERF-1 establish an extended network beneath the apical membrane to which membrane proteins and regulatory components are anchored.
- Subjects
SODIUM cotransport systems; CELLS
- Publication
Kidney International, 2003, Vol 64, Issue 5, p1733
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2003.00266.x