Defective coupling of apical PTH receptors to phospholipase C prevents internalization of the Na+-phosphate cotransporter NaPi-IIa in Nherf1-deficient mice
| Autor: | Marcel Roos, Serge M. Gisler, Jürg Biber, Carsten A. Wagner, Paolo Paola Capuano, Shirish Shenolikar, Brigitte Kaissling, Edward J. Weinman, Gerti Stange, Desa Bacic, Heini Murer |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Sodium-Hydrogen Exchangers Brush border Physiology media_common.quotation_subject 8-Bromo Cyclic Adenosine Monophosphate Parathyroid hormone In Vitro Techniques Biology Sodium-Phosphate Cotransporter Proteins Type IIa Phosphates Diglycerides Kidney Tubules Proximal Mice chemistry.chemical_compound Teriparatide Internal medicine medicine Animals Receptor Internalization Protein Kinase C Receptor Parathyroid Hormone Type 1 media_common Mice Knockout Ion Transport Microvilli Phospholipase C Reabsorption Cell Biology Phosphoproteins Phosphate Cyclic AMP-Dependent Protein Kinases Molecular biology Endocytosis Peptide Fragments Endocrinology chemistry Parathyroid Hormone Type C Phospholipases Female Cotransporter Protein Binding |
| Zdroj: | American Journal of Physiology-Cell Physiology. 292:C927-C934 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00126.2006 |
| Popis: | Phosphate reabsorption in the renal proximal tubule occurs mostly via the type IIa Na+-phosphate cotransporter (NaPi-IIa) in the brush border membrane (BBM). The activity and localization of NaPi-IIa are regulated, among other factors, by parathyroid hormone (PTH). NaPi-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 NaPi-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 NaPi-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 NaPi-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 NaPi-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 NaPi-IIa and, specifically, couples the apical PTHR to PLC. |
| Databáze: | OpenAIRE |
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