Na(+)/H(+) exchanger NHE1 as plasma membrane scaffold in the assembly of signaling complexes

Am J Physiol Cell Physiol. 2004 Oct;287(4):C844-50. doi: 10.1152/ajpcell.00094.2004.


The plasma membrane Na(+)/H(+) exchanger NHE1 has an established function in intracellular pH and cell volume homeostasis by catalyzing electroneutral influx of extracellular Na(+) and efflux of intracellular H(+). A second function of NHE1 as a structural anchor for actin filaments through its direct binding of the ezrin, radixin, and moesin (ERM) family of actin-binding proteins was recently identified. ERM protein binding and actin anchoring by NHE1 are necessary to retain the localization of NHE1 in specialized plasma membrane domains and to promote cytoskeleton-dependent processes, including actin filament bundling and cell-substrate adhesions. This review explores a third function of NHE1, as a plasma membrane scaffold in the assembly of signaling complexes. Through its coordinate functions in H(+) efflux, actin anchoring, and scaffolding, we propose that NHE1 promotes protein interactions and activities, assembles signaling complexes in specialized plasma membrane domains, and coordinates divergent signaling pathways.

Publication types

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

MeSH terms

  • Animals
  • Cation Transport Proteins / physiology*
  • Cell Membrane / physiology*
  • Cytoskeleton / physiology*
  • Humans
  • Membrane Proteins / physiology*
  • Protein Isoforms / physiology
  • Signal Transduction / physiology*
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers / physiology*
  • Structure-Activity Relationship


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