Evidence for functional pre-coupled complexes of receptor heteromers and adenylyl cyclase.
Nat Commun
; 9(1): 1242, 2018 03 28.
Article
em En
| MEDLINE
| ID: mdl-29593213
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Adenilil Ciclases
/
Receptores de Dopamina D2
/
Receptor A2A de Adenosina
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article