ATP Modulates Interaction of Syntaxin-1A with Sulfonylurea Receptor 1 to Regulate Pancreatic β-Cell KATP Channels
| Autor: | Youhou Kang, Yi Zhang, Tao Liang, Show Ling Shyng, Betty Ng, Joseph Chan, Robert G. Tsushima, Huanli Xie, Nathan Chang, Herbert Y. Gaisano, Yuk Man Leung |
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| Rok vydání: | 2011 |
| Předmět: |
endocrine system
Receptors Drug Protein subunit Syntaxin 1 Gating Biology Sulfonylurea Receptors Biochemistry Rats Sprague-Dawley Mice chemistry.chemical_compound Adenosine Triphosphate Adenine nucleotide Membrane Biology Insulin-Secreting Cells Animals Humans Potassium Channels Inwardly Rectifying Receptor Molecular Biology Cell Biology Potassium channel Rats Cell biology Cytosol HEK293 Cells nervous system chemistry Sulfonylurea receptor ATP-Binding Cassette Transporters Ion Channel Gating Adenosine triphosphate hormones hormone substitutes and hormone antagonists Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 286:5876-5883 |
| ISSN: | 0021-9258 |
| Popis: | ATP-sensitive potassium (K(ATP)) channels are regulated by a variety of cytosolic factors (adenine nucleotides, Mg(2+), phospholipids, and pH). We previously reported that K(ATP) channels are also regulated by endogenous membrane-bound SNARE protein syntaxin-1A (Syn-1A), which binds both nucleotide-binding folds of sulfonylurea receptor (SUR)1 and 2A, causing inhibition of K(ATP) channel activity in pancreatic islet β-cells and cardiac myocytes, respectively. In this study, we show that ATP dose-dependently inhibits Syn-1A binding to SUR1 at physiological concentrations, with the addition of Mg(2+) causing a decrease in the ATP-induced inhibitory effect. This ATP disruption of Syn-1A binding to SUR1 was confirmed by FRET analysis in living HEK293 cells. Electrophysiological studies in pancreatic β-cells demonstrated that reduced ATP concentrations increased K(ATP) channel sensitivity to Syn-1A inhibition. Depletion of endogenous Syn-1A in insulinoma cells by botulinum neurotoxin C1 proteolysis followed by rescue with exogenous Syn-1A showed that Syn-1A modulates K(ATP) channel sensitivity to ATP. Thus, our data indicate that although both ATP and Syn-1A independently inhibit β-cell K(ATP) channel gating, they could also influence the sensitivity of K(ATP) channels to each other. These findings provide new insight into an alternate mechanism by which ATP regulates pancreatic β-cell K(ATP) channel activity, not only by its direct actions on Kir6.2 pore subunit, but also via ATP modulation of Syn-1A binding to SUR1. |
| Databáze: | OpenAIRE |
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