Functionally distinct and selectively phosphorylated GPCR subpopulations co-exist in a single cell.
Nat Commun
; 9(1): 1050, 2018 03 13.
Article
en En
| MEDLINE
| ID: mdl-29535304
ABSTRACT
G protein-coupled receptors (GPCRs) transduce pleiotropic intracellular signals in a broad range of physiological responses and disease states. Activated GPCRs can undergo agonist-induced phosphorylation by G protein receptor kinases (GRKs) and second messenger-dependent protein kinases such as protein kinase A (PKA). Here, we characterize spatially segregated subpopulations of ß2-adrenergic receptor (ß2AR) undergoing selective phosphorylation by GRKs or PKA in a single cell. GRKs primarily label monomeric ß2ARs that undergo endocytosis, whereas PKA modifies dimeric ß2ARs that remain at the cell surface. In hippocampal neurons, PKA-phosphorylated ß2ARs are enriched in dendrites, whereas GRK-phosphorylated ß2ARs accumulate in soma, being excluded from dendrites in a neuron maturation-dependent manner. Moreover, we show that PKA-phosphorylated ß2ARs are necessary to augment the activity of L-type calcium channel. Collectively, these findings provide evidence that functionally distinct subpopulations of this prototypical GPCR exist in a single cell.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores Adrenérgicos beta 2
/
Proteínas Quinasas Dependientes de AMP Cíclico
/
Quinasas de Receptores Acoplados a Proteína-G
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos