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Shank2 associates with and regulates Na+/H+ exchanger 3
WonSun Han1, Kyung Hwan Kim, Min Jae Jo
1Department of Pharmacology, Brain Korea 21 Project for Medical Science, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 120-752, Korea.
The Journal of Biological Chemistry
|November 19, 2005
Summary
Shank2 is a newly identified protein that interacts with Na+/H+ exchanger 3 (NHE3). This interaction regulates NHE3
Area of Science:
- Cell Biology
- Physiology
- Molecular Biology
Background:
- Na+/H+ exchanger 3 (NHE3) is crucial for absorbing sodium and bicarbonate in the digestive and renal systems.
- PDZ-based adaptor proteins are known to regulate NHE3 trafficking and activity.
Purpose of the Study:
- To identify novel proteins that interact with NHE3.
- To investigate the role of Shank2 in regulating NHE3 function and expression.
Main Methods:
- Yeast two-hybrid assays to identify interacting proteins.
- Immunoprecipitation and surface plasmon resonance to confirm interactions.
- RNA interference to knock down Shank2 expression in Caco-2 cells.
Main Results:
- Shank2 directly binds to NHE3.
- Overexpression of Shank2 increases NHE3 membrane expression and activity, while reducing cAMP-dependent inhibition.
- Shank2 knockdown decreases NHE3 expression and activity and enhances cAMP-mediated inhibition.
Conclusions:
- Shank2 is a novel NHE3-interacting protein.
- Shank2 plays a key role in regulating NHE3 activity and expression.
- Shank2 influences transepithelial salt and water transport by modulating NHE3 function.