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Am J Physiol Cell Physiol. 2004 Oct;287(4):C844-50.

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

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  • 1University of California, San Francisco, 513 Parnassus Ave., San Francisco, CA 94143, USA.


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.

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