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Diversity of the mammalian sodium/proton exchanger SLC9 gene family

  • The ABC of Solute carriers
  • Guest Editor: Matthias A. Hediger
  • Published:
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Abstract

Sodium/proton antiporters or exchangers (NHE) are integral membrane proteins present in most, if not all, living organisms. In mammals, these transporters chiefly catalyze the electroneutral exchange of Na+ and H+ down their respective concentration gradients and are crucial for numerous physiological processes, ranging from the fine control of intracellular pH and cell volume to systemic electrolyte, acid-base and fluid volume homeostasis. NHE activity also facilitates the progression of other cellular events such as adhesion, migration, and proliferation. Thus far, eight distinct NHE genes (NHE1/SLC9A1–NHE8/SLC9A8) and several pseudogenes have been identified in the human genome. The functional genes encode proteins of varying primary sequence identity (25–70%), but share a common predicted secondary structure comprising 12 conserved membrane-spanning segments at the amino-terminus and a more divergent, cytoplasmically-oriented, carboxy-terminus. They show considerable heterogeneity in their patterns of tissue/cell expression and membrane localization. Functional studies have revealed further differences in their kinetic properties, sensitivity to pharmacological antagonists, and regulation by diverse hormonal and mechanical stimuli. Altered NHE activity has been linked to the pathogenesis of several diseases, including essential hypertension, congenital secretory diarrhea, diabetes, and tissue damage caused by ischemia/reperfusion. Further characterization of their functional properties should lead to a better understanding of their unique contributions to human health and disease.

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Fig. 1A, B.
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Notes

  1. Historically, the term Na+/H+ antiporter (Nha or NHA) is often used when referring to those transporters found in unicellular organisms like bacteria and yeast, whereas in higher eukaryotes the term Na+/H+ exchangers is more commonly used and abbreviated as NHE or NHX, although this is not applied universally.

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Acknowledgements

This study was supported by the Canadian Institutes of Health Research and the Kidney Foundation of Canada. J. O. is a supported by an Investigator Award from the Canadian Institutes of Health Research and is a current holder of a James McGill Professorship. S.G. is cross-appointed to the Department of Biochemistry of the University of Toronto and is the current holder of the Pitblado Chair in Cell Biology.

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  1. Department of Physiology, McGill University, McIntyre Medical Science Bldg. 3655 Promenade Sir-William-Osler, Montreal, Quebec, H3G 1Y6, Canada

    John Orlowski

  2. Programme in Cell Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, M5G 1X8, Canada

    Sergio Grinstein

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Orlowski, J., Grinstein, S. Diversity of the mammalian sodium/proton exchanger SLC9 gene family. Pflugers Arch - Eur J Physiol 447, 549–565 (2004). https://doi.org/10.1007/s00424-003-1110-3

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