title: Interactions of MAP17 with the NaPi-IIa/PDZK1 protein complex in renal proximal tubular cells.
abstract: An essential role in phosphate homeostasis is played by Na/Pi cotransporter IIa that is localized in the brush borders of renal proximal tubular cells. Recent studies identified several PDZ proteins interacting with the COOH-terminal tail of NaPi-IIa, such as PDZK1 and NHERF-1. Here, by using yeast two-hybrid screen of mouse kidney cDNA library, we attempted to find proteins interacting with the NH2-terminal part of NaPi-IIa. We identified MAP17, a 17-kDa membrane protein that has been described to be associated with various human carcinomas, but it is also expressed in normal kidneys. Results obtained by various in vitro analyses suggested that MAP17 interacts with the fourth domain of PDZK1 but not with other PDZ proteins localized in proximal tubular brush borders. As revealed by immunofluorescence, MAP17 was abundant in S1 but almost absent in S3 segments. No alterations of the apical abundance of MAP17 were observed after maneuvers undertaken to change the content of NaPi-IIa (parathyroid hormone treatment, different phosphate diets). In agreement, no change in the amount of MAP17 mRNA was observed. Results obtained from transfection studies using opossum kidney cells indicated that the apical localization of MAP17 is independent of PDZK1 but that MAP17 is required for apical localization of PDZK1. In summary, we conclude that MAP17 1) interacts with PDZK1 only, 2) associates with the NH2 terminus of NaPi-IIa within the PDZK1/NaPi-IIa/MAP17 complex, and 3) acts as an apical anchoring site for PDZK1.
authors.affiliation: Institute of Physiology, University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pribanic
authors.forename: Serge Mike
authors.initials: SM
authors.lastname: Gisler
authors.forename: Desa
authors.initials: D
authors.lastname: Bacic
authors.forename: Caveh
authors.initials: C
authors.lastname: Madjdpour
authors.forename: Nati
authors.initials: N
authors.lastname: Hernando
authors.forename: Victor
authors.initials: V
authors.lastname: Sorribas
authors.forename: Andrea
authors.initials: A
authors.lastname: Gantenbein
authors.forename: Jürg
authors.initials: J
authors.lastname: Biber
authors.forename: Heini
authors.initials: H
authors.lastname: Murer
mesh_terms: D000818:Animals; D002460:Cell Line; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009363:Neoplasm Proteins; D009893:Opossums; D050608:Sodium-Phosphate Cotransporter Proteins; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D027981:Symporters / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; C509768:PDZK1IP1 protein, human; C509767:Pdzk1ip1 protein, mouse; C493555:Slc34a1 protein, mouse; D050608:Sodium-Phosphate Cotransporter Proteins; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D027981:Symporters