Format

Send to

Choose Destination
Sci Rep. 2019 Feb 8;9(1):1718. doi: 10.1038/s41598-018-37222-1.

The in vivo specificity of synaptic Gβ and Gγ subunits to the α2a adrenergic receptor at CNS synapses.

Author information

1
Department of Pharmacology, Vanderbilt University, Nashville, TN, 37232-6600, USA.
2
Geisel School of Medicine at Dartmouth, 1 Rope Ferry Road, Hanover, NH, 03755, USA.
3
Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN, 37232-6600, USA.
4
Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, 79104, Freiburg, Germany.
5
Department of Cell, Development, and Integrative Biology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, 35294-3412, USA.
6
Department of Pharmacology, Vanderbilt University, Nashville, TN, 37232-6600, USA. heidi.hamm@vanderbilt.edu.

Abstract

G proteins are major transducers of signals from G-protein coupled receptors (GPCRs). They are made up of α, β, and γ subunits, with 16 Gα, 5 Gβ and 12 Gγ subunits. Though much is known about the specificity of Gα subunits, the specificity of Gβγs activated by a given GPCR and that activate each effector in vivo is not known. Here, we examined the in vivo Gβγ specificity of presynaptic α2a-adrenergic receptors (α2aARs) in both adrenergic (auto-α2aARs) and non-adrenergic neurons (hetero-α2aARs) for the first time. With a quantitative MRM proteomic analysis of neuronal Gβ and Gγ subunits, and co-immunoprecipitation of tagged α2aARs from mouse models including transgenic FLAG-α2aARs and knock-in HA-α2aARs, we investigated the in vivo specificity of Gβ and Gγ subunits to auto-α2aARs and hetero-α2aARs activated with epinephrine to understand the role of Gβγ specificity in diverse physiological functions such as anesthetic sparing, and working memory enhancement. We detected Gβ2, Gγ2, Gγ3, and Gγ4 with activated auto α2aARs, whereas we found Gβ4 and Gγ12 preferentially interacted with activated hetero-α2aARs. Further understanding of in vivo Gβγ specificity to various GPCRs offers new insights into the multiplicity of genes for Gβ and Gγ, and the mechanisms underlying GPCR signaling through Gβγ subunits.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center