G Protein Activation by Serotonin Type 4 Receptor Dimers
| Autor: | Jean-Philippe Pin, Aline Dumuis, Lucie P. Pellissier, Jean-Louis Banères, Eric Trinquet, Elisabeth Cassier, Philippe Marin, Sylvie Claeysen, Florence Gaven, Joël Bockaert, Gael Barthet |
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| Rok vydání: | 2011 |
| Předmět: |
0303 health sciences
Gs alpha subunit G protein Class C GPCR Cell Biology GPCR oligomer Biology Biochemistry Rhodopsin-like receptors 03 medical and health sciences 0302 clinical medicine Heterotrimeric G protein Receptor Molecular Biology 030217 neurology & neurosurgery 030304 developmental biology G protein-coupled receptor |
| Zdroj: | Journal of Biological Chemistry. 286:9985-9997 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m110.201939 |
| Popis: | The discovery that class C G protein-coupled receptors (GPCRs) function as obligatory dimeric entities has generated major interest in GPCR oligomerization. Oligomerization now appears to be a common feature among all GPCR classes. However, the functional significance of this process remains unclear because, in vitro, some monomeric GPCRs, such as rhodopsin and β2-adrenergic receptors, activate G proteins. By using wild type and mutant serotonin type 4 receptors (5-HT4Rs) (including a 5-HT4-RASSL) expressed in COS-7 cells as models of class A GPCRs, we show that activation of one protomer in a dimer was sufficient to stimulate G proteins. However, coupling efficiency was 2 times higher when both protomers were activated. Expression of combinations of 5-HT4, in which both protomers were able to bind to agonists but only one could couple to G proteins, suggested that upon agonist occupancy, protomers did not independently couple to G proteins but rather that only one G protein was activated. Coupling of a single heterotrimeric Gs protein to a receptor dimer was further confirmed in vitro, using the purified recombinant WT RASSL 5-HT4R obligatory heterodimer. These results, together with previous findings, demonstrate that, differently from class C GPCR dimers, class A GPCR dimers have pleiotropic activation mechanisms. |
| Databáze: | OpenAIRE |
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