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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Ao Shen, Madeline Nieves-Cintron, Yawen Deng, Qian Shi, Dhrubajyoti Chowdhury, Jinyi Qi, Johannes W. Hell, Manuel F. Navedo, Yang K. Xiang

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 2AR) 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. More... »

PAGES

1050

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-018-03459-7

DOI

http://dx.doi.org/10.1038/s41467-018-03459-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1101459012

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29535304


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