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The role of NHERF-1 in the regulation of renal proximal tubule sodium-hydrogen exchanger 3 and sodium-dependent phosphate cotransporter 2a.

Publication ,  Journal Article
Weinman, EJ; Cunningham, R; Wade, JB; Shenolikar, S
Published in: J Physiol
August 15, 2005

Adaptor proteins containing PDZ interactive domains have been recently identified to regulate the trafficking and activity of ion transporters and channels in epithelial tissue. In the renal proximal tubule, three PDZ adaptor proteins, namely NHERF-1, NHERF-2 and PDZK1, are expressed in the apical membrane, heterodimerize with one another, and, at least in vitro, are capable of binding to NHE3 and Npt2a, two major regulated renal proximal tubule apical membrane transporters. Studies using NHERF-1 null mice have begun to provide insights into the organization of these adaptor proteins and their specific interactions with NHE3 and Npt2a. Experiments using brush border membranes and cultured renal proximal tubule cells indicate a specific requirement for NHERF-1 for cAMP-mediated phosphorylation and inhibition of NHE3. NHERF-1 null mice demonstrate increased urinary excretion of phosphate associated with mistargeting of Npt2a to the apical membrane of renal proximal tubule cells. NHERF-1 null animals challenged with a low phosphate diet and proximal tubule cells from these animals cultured in a low phosphate media fail to adapt as well as wild-type mice. These studies indicate a unique requirement for NHERF-1 in cAMP regulation of NHE3 and in the trafficking of Npt2a.

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Published In

J Physiol

DOI

ISSN

0022-3751

Publication Date

August 15, 2005

Volume

567

Issue

Pt 1

Start / End Page

27 / 32

Location

England

Related Subject Headings

  • Symporters
  • Sodium-Phosphate Cotransporter Proteins
  • Sodium-Hydrogen Exchangers
  • Sodium-Hydrogen Exchanger 3
  • Physiology
  • Phosphoproteins
  • Kidney Tubules, Proximal
  • Humans
  • Animals
  • 42 Health sciences
 

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Weinman, E. J., Cunningham, R., Wade, J. B., & Shenolikar, S. (2005). The role of NHERF-1 in the regulation of renal proximal tubule sodium-hydrogen exchanger 3 and sodium-dependent phosphate cotransporter 2a. J Physiol, 567(Pt 1), 27–32. https://doi.org/10.1113/jphysiol.2005.086777
Weinman, Edward J., Rochelle Cunningham, James B. Wade, and Shirish Shenolikar. “The role of NHERF-1 in the regulation of renal proximal tubule sodium-hydrogen exchanger 3 and sodium-dependent phosphate cotransporter 2a.J Physiol 567, no. Pt 1 (August 15, 2005): 27–32. https://doi.org/10.1113/jphysiol.2005.086777.
Weinman, Edward J., et al. “The role of NHERF-1 in the regulation of renal proximal tubule sodium-hydrogen exchanger 3 and sodium-dependent phosphate cotransporter 2a.J Physiol, vol. 567, no. Pt 1, Aug. 2005, pp. 27–32. Pubmed, doi:10.1113/jphysiol.2005.086777.
Journal cover image

Published In

J Physiol

DOI

ISSN

0022-3751

Publication Date

August 15, 2005

Volume

567

Issue

Pt 1

Start / End Page

27 / 32

Location

England

Related Subject Headings

  • Symporters
  • Sodium-Phosphate Cotransporter Proteins
  • Sodium-Hydrogen Exchangers
  • Sodium-Hydrogen Exchanger 3
  • Physiology
  • Phosphoproteins
  • Kidney Tubules, Proximal
  • Humans
  • Animals
  • 42 Health sciences