Intracellular calcium levels determine differential modulation of allosteric interactions within G protein-coupled receptor heteromers
| Autor: | Navarro, G., Aguinaga, D., Hradsky, J., Moreno, E., Reddy, P.P., Cortés, A., Mallol, J., Casadó, V., Mikhaylova, Marina, Kreutz, M.R., Lluís, C., Canela, E.I., McCormick, P.J., Ferreira, S., Ferré, S., Sub Cell Biology, Celbiologie |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Adenosine A2 Receptor Agonists
Receptor Adenosine A2A Recombinant Fusion Proteins Neuronal Calcium-Sensor Proteins Allosteric regulation Clinical Biochemistry Heteromer Adenosine A2A receptor Biology Biochemistry Article Rats Sprague-Dawley Calmodulin Dopamine receptor D2 Drug Discovery Extracellular medicine Animals Humans Phosphorylation Molecular Biology Cells Cultured G protein-coupled receptor Mitogen-Activated Protein Kinase 1 Neurons Pharmacology Mitogen-Activated Protein Kinase 3 Receptors Dopamine D2 Neuropeptides General Medicine Adenosine Rats Cell biology HEK293 Cells Molecular Medicine Calcium Mitogen-Activated Protein Kinases Intracellular Adenylyl Cyclases Signal Transduction medicine.drug |
| Zdroj: | Chemistry & Biology, 21(11), 1546. Elsevier Chem Biol |
| ISSN: | 1074-5521 |
| Popis: | The pharmacological significance of the adenosine A(2A) receptor (A(2A)R)-dopamine D(2) receptor (D(2)R) heteromer is well established and it is being considered as an important target for the treatment of Parkinson’s disease and other neuropsychiatric disorders. However, the physiological factors that control its distinctive biochemical properties are still unknown. We demonstrate that different intracellular Ca(2+) levels exert a differential modulation of A(2A)R-D(2)R heteromer-mediated adenylyl-cyclase and MAPK signaling in striatal cells. This depends on the ability of low and high Ca(2+) levels to promote a selective interaction of the heteromer with the neuronal Ca(2+)-binding proteins NCS-1 and calneuron-1, respectively. These Ca(2+)-binding proteins differentially modulate allosteric interactions within the A(2A)R-D(2)R heteromer, which constitutes a unique cellular device that integrates extracellular (adenosine and dopamine) and intracellular (Ca(+2)) signals to produce a specific functional response. |
| Databáze: | OpenAIRE |
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