Physiological Functions and Regulation of the Na+/H+ Exchanger [NHE1] in Renal Tubule Epithelial Cells

Kidney Blood Press Res. 2015;40(5):452-66. doi: 10.1159/000368521. Epub 2015 Aug 25.

Abstract

The sodium-hydrogen exchanger isoform-1 [NHE1] is a ubiquitously expressed plasma membrane protein that plays a central role in intracellular pH and cell volume homeostasis by catalyzing an electroneutral exchange of extracellular sodium and intracellular hydrogen. Outside of this important physiological function, the NHE1 cytosolic tail domain acts as a molecular scaffold regulating cell survival and actin cytoskeleton organization through NHE1-dependent signaling proteins. NHE1 plays main roles in response to physiological stress conditions which in addition to cell shrinkage and acidification, include hypoxia and mechanical stimuli, such as cell stretch. NHE1-mediated modulation of programmed cell death results from the exchanger-mediated changes in pHi, cell volume, and/or [Na+]I; and, it has recently become known that regulation of cellular signaling pathways are involved as well. This review focuses on NHE1 functions and regulations. We describe evidence showing how these structural actions integrate with ion translocation in regulating renal tubule epithelial cell survival.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cation Transport Proteins / physiology*
  • Cell Size
  • Cell Survival / physiology
  • Epithelial Cells / physiology*
  • Humans
  • Ion Transport / physiology
  • Kidney Tubules / cytology*
  • Kidney Tubules / physiology*
  • Signal Transduction / physiology
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers / physiology*

Substances

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