Journal
EMBO JOURNAL
Volume 30, Issue 4, Pages 679-691Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2010.356
Keywords
Na+/H+ exchange; pH regulation; surface charge
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Funding
- Canadian Institute of Health Research (CIHR)
- Kidney Foundation of Canada
- Canadian Society of Nephrology
- Heart and Stroke Foundation of Canada
- Pitblado Chair in Cell Biology
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The Na+/H+ exchanger NHE3 plays a central role in intravascular volume and acid-base homeostasis. Ion exchange activity is conferred by its transmembrane domain, while regulation of the rate of transport by a variety of stimuli is dependent on its cytosolic C-terminal region. Liposome-and cell-based assays employing synthetic or recombinant segments of the cytosolic tail demonstrated preferential association with anionic membranes, which was abrogated by perturbations that interfere with electrostatic interactions. Resonance energy transfer measurements indicated that segments of the C-terminal domain approach the bilayer. In intact cells, neutralization of basic residues in the cytosolic tail by mutagenesis or disruption of electrostatic interactions inhibited Na+/H+ exchange activity. An electrostatic switch model is proposed to account for multiple aspects of the regulation of NHE3 activity. The EMBO Journal (2011) 30, 679-691. doi:10.1038/emboj.2010.356; Published online 18 January 2011
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