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Nat Commun. 2018 Mar 13;9(1):1050. doi: 10.1038/s41467-018-03459-7.

Functionally distinct and selectively phosphorylated GPCR subpopulations co-exist in a single cell.

Author information

1
Department of Pharmacology, University of California Davis, Davis, CA, 95616, USA.
2
The Second Affiliated Hospital, Sun Yat-sen University, 510120, Guangzhou, China.
3
Department of Biomedical Engineering, University of California Davis, Davis, CA, 95616, USA.
4
Department of Pharmacology, University of California Davis, Davis, CA, 95616, USA. ykxiang@ucdavis.edu.
5
VA Northern California Health Care System, Mather, CA, 95655, USA. ykxiang@ucdavis.edu.

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 β2-adrenergic receptor (β2AR) undergoing selective phosphorylation by GRKs or PKA in a single cell. GRKs primarily label monomeric β2ARs that undergo endocytosis, whereas PKA modifies dimeric β2ARs that remain at the cell surface. In hippocampal neurons, PKA-phosphorylated β2ARs are enriched in dendrites, whereas GRK-phosphorylated β2ARs accumulate in soma, being excluded from dendrites in a neuron maturation-dependent manner. Moreover, we show that PKA-phosphorylated β2ARs 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.

PMID:
29535304
PMCID:
PMC5849717
DOI:
10.1038/s41467-018-03459-7
[Indexed for MEDLINE]
Free PMC Article

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