Na(+)/H(+) exchanger NHE1 as plasma membrane scaffold in the assembly of signaling complexes.
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.
Baumgartner
Martin
M
University of California, San Francisco, 513 Parnassus Ave., San Francisco, CA 94143, USA.
Patel
Hitesh
H
Barber
Diane L
DL
D000818:Animals; D027682:Cation Transport Proteins / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D020033:Protein Isoforms / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*; D013329:Structure-Activity Relationship
D027682:Cation Transport Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers