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

Ao Shen, Madeline Nieves-Cintron, Yawen Deng, Qian Shi, Dhrubajyoti Chowdhury, Jinyi Qi, Johannes W. Hell, Manuel F. Navedo and Yang K. Xiang ()
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Ao Shen: University of California Davis
Madeline Nieves-Cintron: University of California Davis
Yawen Deng: University of California Davis
Qian Shi: University of California Davis
Dhrubajyoti Chowdhury: University of California Davis
Jinyi Qi: University of California Davis
Johannes W. Hell: University of California Davis
Manuel F. Navedo: University of California Davis
Yang K. Xiang: University of California Davis

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03459-7

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