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NHERF and regulation of the renal sodium-hydrogen exchanger NHE3

Pflügers Archiv volume 450, pages 137–144 (2005)Cite this article

Abstract

The sodium-hydrogen exchanger 3 (NHE3) isoform is the major regulated sodium transporter in the proximal convoluted tubule of the kidney. Study of the regulation of NHE3 by hormonal stimuli has identified a number of PDZ adaptor proteins that form an apical/subapical membrane scaffold that binds NHE3 and facilitates down-regulation of its activity in response to cAMP and activation of protein kinase A. The precise relation of proximal tubule adaptor proteins such as sodium-hydrogen exchanger regulatory factor-1 (NHERF-1), NHERF-2, and PDZ domain-containing-protein-1 (PDZK1) with each other and with protein targets such as NHE3 has been evolving with the development of specific reagents and genetically altered animals. In this review, we trace the discovery of NHERF-1 and NHERF-2, and update our current understanding of the relation between these proteins and the regulation and trafficking of NHE3.

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Acknowledgements

Deborah Steplock and James B. Wade PhD made significant contributions to the performance of many of the experiments and their contributions are acknowledged. These studies were supported by grants from the National Institutes of Health (DK55881) and Research Service, Department of Veterans Affairs.

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Affiliations

  1. Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    Edward J. Weinman & Rochelle Cunningham

  2. Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    Edward J. Weinman

  3. Medical Service, Department of Veterans Affairs Medical Center, Baltimore, MD, 21201, USA

    Edward J. Weinman

  4. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, 27710, USA

    Shirish Shenolikar

Authors
  1. Edward J. Weinman
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  2. Rochelle Cunningham
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  3. Shirish Shenolikar
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Correspondence to Edward J. Weinman.

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Weinman, E.J., Cunningham, R. & Shenolikar, S. NHERF and regulation of the renal sodium-hydrogen exchanger NHE3. Pflugers Arch - Eur J Physiol 450, 137–144 (2005). https://doi.org/10.1007/s00424-005-1384-8

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  • DOI: https://doi.org/10.1007/s00424-005-1384-8

Keywords

  • PDZ adaptor proteins
  • NHERF-1
  • NHERF-2
  • Renal sodium reabsorption
  • NHE3