title: NHERF-1 and the regulation of renal phosphate reabsoption: a tale of three hormones.
abstract: The renal excretion of inorganic phosphate is regulated in large measure by three hormones, namely, parathyroid hormone, dopamine, and fibroblast growth factor-23. Recent experiments have indicated that the major sodium-dependent phosphate transporter in the renal proximal tubule, Npt2a, binds to the adaptor protein sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) and in the absence of NHERF-1, the inhibitory effect of these three hormones is absent. From these observations, a new model for the hormonal regulation of renal phosphate transport was developed. The downstream signaling pathways of these hormones results in the phosphorylation of the PDZ 1 domain of NHERF-1 and the dissociation of Npt2a/NHERF-1 complexes. In turn, this dissociation facilitates the endocytosis of Npt2a with a subsequent decrease in the apical membrane abundance of the transporter and a decrease in phosphate reabsorption. The current review outlines the experimental observations supporting the operation of this unique regulatory system.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. eweinman@medicine.umaryland.edu
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Weinman
authors.forename: Eleanor D
authors.initials: ED
authors.lastname: Lederer
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008958:Models, Molecular; D054731:PDZ Domains / Q000502:physiology; D010281:Parathyroid Hormone / Q000502:physiology*; D010710:Phosphates / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D011487:Protein Conformation; D015398:Signal Transduction / Q000187:drug effects; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000378:metabolism
chemical_list: D006728:Hormones; D010281:Parathyroid Hormone; D010710:Phosphates; D010750:Phosphoproteins; C493554:SLC34A1 protein, human; D017923:Sodium-Hydrogen Exchangers; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; C093376:sodium-hydrogen exchanger regulatory factor; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D004298:Dopamine