Multiple Modes of Regulation of Na+/H+ Exchangers

Authors

  • HISAYOSHI HAYASHI,

    1. Cell Biology Programme, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada
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    • a

      Contributed equally to the study.

  • KATALIN SZÁSZI,

    1. Cell Biology Programme, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada
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      Contributed equally to the study.

  • SERGIO GRINSTEIN

    Corresponding author
    1. Cell Biology Programme, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada
      Address for correspondence: Dr. Sergio Grinstein, Cell Biology Programme, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G1X8, Canada. Voice: 416-813-5727; fax: 416-813-5028; sga@sickkids.on.ca.
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Address for correspondence: Dr. Sergio Grinstein, Cell Biology Programme, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G1X8, Canada. Voice: 416-813-5727; fax: 416-813-5028; sga@sickkids.on.ca.

Abstract

Abstract: Mammalian Na+/H+ exchangers (NHE) mediate electroneutral countertransport of H+ for Na+ across the plasmalemmal and organellar membranes. They contribute to cellular and organellar pH and volume regulation and transepithelial Na+ transport. The aim of this review is to illustrate the complex regulation of these transporters by focusing on the multiple mechanisms controlling the epithelial isoform, NHE3. A variety of agents and conditions (e.g., hormones, growth factors, cellular pH, and medium osmolarity) act in concert to achieve short-term and long-term regulation of this isoform. The underlying mechanism involves changes in the number of transporters on the cell surface and/or altered activity of the individual exchangers due to allosteric activation by intracellular protons, phosphorylation and interaction with accessory proteins and the cytoskeleton. A similar regulatory versatility probably applies to other NHE isoforms, and the lessons learned from studying members of the NHE family could serve as a useful reference when exploring the modes and levels of regulation of other transporters.

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