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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/122379
Evidence for functional pre-coupled complexes of receptor heteromers and adenylyl cyclase
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G protein-coupled receptors (GPCRs), G proteins and adenylyl cyclase (AC) comprise one of the most studied transmembrane cell signaling pathways. However, it is unknown whether the ligand-dependent interactions between these signaling molecules are based on random collisions or the rearrangement of pre-coupled elements in a macromolecular complex. Furthermore, it remains controversial whether a GPCR homodimer coupled to a single heterotrimeric G protein constitutes a common functional unit. Using a peptide-based approach, we here report evidence for the existence of functional pre-coupled complexes of heteromers of adenosine A2A receptor and dopamine D2 receptor homodimers coupled to their cognate Gs and Gi proteins and to subtype 5 AC. We also demonstrate that this macromolecular complex provides the necessary frame for the canonical Gs-Gi interactions at the AC level, sustaining the ability of a Gi-coupled GPCR to counteract AC activation mediated by a Gs-coupled GPCR.
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NAVARRO BRUGAL, Gemma, et al. Evidence for functional pre-coupled complexes of receptor heteromers and adenylyl cyclase. Nature Communications. 2018. Vol. 9, num. 1, pags. 1242. ISSN 2041-1723. [consulted: 6 of June of 2026]. Available at: https://hdl.handle.net/2445/122379