Membrane surface charge dictates the structure and function of the epithelial Na+/H+ exchanger
Robert Todd Alexander1, Valentin Jaumouillé, Tony Yeung
1Cell Biology Program, The Hospital for Sick Children, Toronto, Canada.
The EMBO Journal
|January 20, 2011
Summary
The Na(+)/H(+) exchanger NHE3
Area of Science:
- Physiology
- Biochemistry
- Molecular Biology
Background:
- The Na(+)/H(+) exchanger NHE3 is crucial for maintaining blood volume and pH balance.
- Its transport activity is regulated by the cytosolic C-terminal region.
Purpose of the Study:
- To investigate the role of electrostatic interactions in the regulation of NHE3 activity.
- To elucidate the mechanism by which the C-terminal region interacts with membranes.
Main Methods:
- Liposome- and cell-based assays were used to study membrane association.
- Resonance energy transfer measured the proximity of C-terminal segments to the bilayer.
- Mutagenesis studies altered basic residues in the cytosolic tail.
Main Results:
- NHE3 C-terminal segments preferentially bind to anionic membranes via electrostatic interactions.
- Disrupting these interactions inhibits NHE3 activity.
- Mutagenesis of basic residues also reduced ion exchange activity.
Conclusions:
- Electrostatic interactions are critical for NHE3 regulation.
- An electrostatic switch model explains the regulation of NHE3 activity by its C-terminal region.
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