NHERF-1 and the regulation of renal phosphate reabsoption: A tale of three hormones

Edward J. Weinman, Eleanor D. Lederer

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)F321-F327
JournalAmerican Journal of Physiology - Renal Physiology
Issue number3
StatePublished - Aug 1 2012
Externally publishedYes


  • Dopamine
  • FGF-23
  • Parathyroid hormone

ASJC Scopus subject areas

  • Physiology
  • Urology


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