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; Yang K Xiang

doi:10.1038/s41467-018-03459-7

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

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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

Nature communications, Vol.9(1), pp.1050-12

03/13/2018

DOI: 10.1038/s41467-018-03459-7

PMCID: PMC5849717

PMID: 29535304

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

Animals

Calcium Channels, L-Type - metabolism

Cyclic AMP-Dependent Protein Kinases - metabolism

G-Protein-Coupled Receptor Kinases - metabolism

HEK293 Cells

Hippocampus - metabolism

Humans

Mice

Neurons - metabolism

Phosphorylation

Receptors, Adrenergic, beta-2 - metabolism

Single Molecule Imaging

Single-Cell Analysis

Details

Title: Subtitle: Functionally distinct and selectively phosphorylated GPCR subpopulations co-exist in a single cell
Creators: 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
Resource Type: Journal article
Publication Details: Nature communications, Vol.9(1), pp.1050-12
DOI: 10.1038/s41467-018-03459-7
PMID: 29535304
PMCID: PMC5849717
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Grant note: R01 NS078792 / NINDS NIH HHS T32 GM099608 / NIGMS NIH HHS R01 HL127764 / NHLBI NIH HHS R01 AG055357 / NIA NIH HHS R01 HL121059 / NHLBI NIH HHS R01 HL098200 / NHLBI NIH HHS R01 HL112413 / NHLBI NIH HHS R01 GM129376 / NIGMS NIH HHS I01 BX002900 / BLRD VA
Language: English
Date published: 03/13/2018
Academic Unit: Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984359826102771

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