Na+-H+ exchanger-1 (NHE1) regulation in kidney proximal tubule

Cell Mol Life Sci. 2015 Jun;72(11):2061-74. doi: 10.1007/s00018-015-1848-8. Epub 2015 Feb 14.


The ubiquitously expressed plasma membrane Na(+)-H(+) exchanger NHE1 is a 12 transmembrane-spanning protein that directs important cell functions such as homeostatic intracellular volume and pH control. The 315 amino acid cytosolic tail of NHE1 binds plasma membrane phospholipids and multiple proteins that regulate additional, ion-translocation independent functions. This review focuses on NHE1 structure/function relationships, as well as the role of NHE1 in kidney proximal tubule functions, including pH regulation, vectorial Na(+) transport, cell volume control and cell survival. The implications of these functions are particularly critical in the setting of progressive, albuminuric kidney diseases, where the accumulation of reabsorbed fatty acids leads to disruption of NHE1-membrane phospholipid interactions and tubular atrophy, which is a poor prognostic factor for progression to end stage renal disease. This review amplifies the vital role of the proximal tubule NHE1 Na(+)-H(+) exchanger as a kidney cell survival factor.

Publication types

  • Review

MeSH terms

  • Acute Kidney Injury / pathology
  • Amino Acid Sequence
  • Animals
  • Cation Transport Proteins / metabolism*
  • Cell Membrane / metabolism*
  • Cell Survival
  • Humans
  • Ion Transport
  • Kidney Failure, Chronic / enzymology
  • Kidney Tubules, Proximal / metabolism*
  • Membrane Proteins / metabolism*
  • Mice
  • Models, Animal
  • Protein Binding
  • Protein Structure, Tertiary
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers / metabolism*


  • Cation Transport Proteins
  • Membrane Proteins
  • SLC9A1 protein, human
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers