Functionally distinct and selectively phosphorylated GPCR subpopulations co-exist in a single cell
Year: 2018
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: Coupling of vascular CaV1.2 channels in health and disease, Predoctoral Training in Pharmacological Sciences, Calcium Sparklers-Induced Vascular Dysfunction During Diabetes, Signaling by cAMP within Postsynaptic Nanodomains, Novel mechanism on subpopulation-dependent biased GPCR signaling in neurons, Dysregulation of Cav1.2 by beta amyloid peptide, Insulin Inhibition of beta-AR Signaling in the Myocardium, G7737658675, Cardiac Dysfunction in the Met Syndrome: Cross-talk between IR and bAR Signaling, Dysregulation of Cav1.2 by beta amyloid peptide
OpenAlex ID: W2789807888