期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-03459-7
关键词
-
资金
- NIH [HL127764, HL112413, 01BX002900, HL098200, HL121059, NS078792, AG055357]
- American Heart Association postdoctoral fellowship
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 beta(2)-adrenergic receptor (beta(2)AR) undergoing selective phosphorylation by GRKs or PKA in a single cell. GRKs primarily label monomeric beta(2)ARs that undergo endocytosis, whereas PKA modifies dimeric beta(2)ARs that remain at the cell surface. In hippocampal neurons, PKA-phosphorylated beta(2)ARs are enriched in dendrites, whereas GRK-phosphorylated beta(2)ARs accumulate in soma, being excluded from dendrites in a neuron maturation-dependent manner. Moreover, we show that PKA-phosphorylated beta(2)ARs 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.
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