Details

Autor(en) / Beteiligte

• Capuano, Paola
• Bacic, Desa
• Roos, Marcel
• Gisler, Serge M.
• Stange, Gerti
• Biber, Jürg
• Kaissling, Brigitte
• Weinman, Edward J.
• Shenolikar, Shirish
• Wagner, Carsten A.
• Murer, Heini

Titel

Defective coupling of apical PTH receptors to phospholipase C prevents internalization of the Na + -phosphate cotransporter NaP i -IIa in Nherf1 -deficient mice

Ist Teil von

• American Journal of Physiology: Cell Physiology, 2007-02, Vol.292 (2), p.C927-C934

Erscheinungsjahr

2007

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Phosphate reabsorption in the renal proximal tubule occurs mostly via the type IIa Na + -phosphate cotransporter (NaP i -IIa) in the brush border membrane (BBM). The activity and localization of NaP i -IIa are regulated, among other factors, by parathyroid hormone (PTH). NaP i -IIa interacts in vitro via its last three COOH-terminal amino acids with the PDZ protein Na + /H + -exchanger isoform 3 regulatory factor (NHERF)-1 (NHERF1). Renal phosphate reabsorption in Nherf1-deficient mice is altered, and NaP i -IIa expression in the BBM is reduced. In addition, it has been proposed that NHERF1 and NHERF2 are important for the coupling of PTH receptors (PTHRs) to phospholipase C (PLC) and the activation of the protein kinase C pathway. We tested the role of NHERF1 in the regulation of NaP i -IIa by PTH in Nherf1-deficient mice. Immunohistochemistry and Western blotting demonstrated that stimulation of apical and basolateral receptors with PTH-(1–34) led to internalization of NaP i -IIa in wild-type and Nherf1-deficient mice. Stimulation of only apical receptors with PTH-(3–34) failed to induce internalization in Nherf1-deficient mice. Expression and localization of apical PTHRs were similar in wild-type and Nherf1-deficient mice. Activation of the protein kinase C- and A-dependent pathways with 1,2-dioctanoyl- sn-glycerol or 8-bromo-cAMP induced normal internalization of NaP i -IIa in wild-type, as well as Nherf1-deficient, mice. Stimulation of PLC activity due to apical PTHRs was impaired in Nherf1-deficient mice. These data suggest that NHERF1 in the proximal tubule is important for PTH-induced internalization of NaP i -IIa and, specifically, couples the apical PTHR to PLC.