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G alpha 13 stimulates Na-H exchange
T Voyno-Yasenetskaya1, B R Conklin, R L Gilbert
1Department of Medicine, University of California, San Francisco 94143.
The Journal of Biological Chemistry
|February 18, 1994
Summary
The G protein alpha 13 subunit activates the sodium-hydrogen exchanger 1 (NHE1). This newly identified signaling pathway for alpha 13 provides a novel mechanism for regulating cellular pH balance.
Area of Science:
- Cellular Physiology
- Molecular Biology
- G Protein Signaling
Background:
- The ubiquitous sodium-hydrogen exchanger 1 (NHE1) is crucial for maintaining intracellular pH and is regulated by various signaling pathways.
- Previous research established that Gs-coupled receptors stimulating adenylyl cyclase activate NHE1 via a mechanism independent of direct receptor-G protein coupling.
Purpose of the Study:
- To investigate the role of the G protein alpha 13 subunit in the regulation of NHE1 activity.
- To identify novel signaling pathways involved in NHE1 regulation.
Main Methods:
- Transient expression of wild-type and mutationally activated alpha 13 subunits in cells.
- Construction and expression of an alpha 13/alpha z chimera to study Gi-coupled receptor activation.
- Assays for Na-H exchange activity, adenylyl cyclase activity, and phosphoinositide hydrolysis.
Main Results:
- Mutationally activated alpha 13 constitutively stimulates Na-H exchange.
- An alpha 13/alpha z chimera mediates stimulation of Na-H exchange by the dopamine2 receptor (a Gi-coupled receptor).
- Activated alpha 13 does not affect adenylyl cyclase activity or phosphoinositide hydrolysis, indicating pathway independence.
Conclusions:
- The G protein alpha 13 subunit is a novel activator of the sodium-hydrogen exchanger 1 (NHE1).
- This study reveals the first signaling function of alpha 13, linking it to cellular pH regulation.
- A new G protein-dependent pathway for NHE1 regulation, independent of adenylyl cyclase and phosphoinositide hydrolysis, has been identified.