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G protein specificity of inhibitory adrenergic a 2a receptor‐mediated modulation of synaptic transmission
Author(s) -
Yim Yun Young,
Betke Katherine,
McDonald W. Hayes,
Gilsbach Ralf,
Chen Yunjia,
Hyde Karren,
Wang Qin,
Hein Lutz,
Hamm Heidi
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb566
Subject(s) - neurotransmission , g protein coupled receptor , exocytosis , microbiology and biotechnology , receptor , neurotransmitter , neuroscience , neurotransmitter receptor , adrenergic , chemistry , immunoprecipitation , munc 18 , inhibitory postsynaptic potential , g protein , biology , secretion , synaptic vesicle , biochemistry , vesicle , gene , membrane
Modulation of neurotransmitter exocytosis by activated Gi/o‐type G‐protein coupled receptors (GPCRs) is a universal regulatory mechanism used both to avoid overstimulation and to influence circuitry. One of the known modulation mechanisms is Gβγ and soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) complex interaction. There are 5 Gβ and 12 Gγ subunits, but specific Gβγs activated by a given GPCR in vivo are not known. Presynaptic α 2a ‐adrenergic receptors (α 2a ‐ARs) in both adrenergic (auto α 2a ‐ARs) and non‐adrenergic neurons (hetero α 2a ‐ARs) inhibit neurotransmitter release and affect various physiological function such as anesthetic sparing and working memory enhancement. Here, we investigate whether auto α 2a ‐ARs in sympathetic neurons use the same Gbg subunits as hetero α 2a ‐ARs in other neuronal types to inhibit exocytosis by interacting with SNARE. Using several mice models including transgenic Flag‐α 2a ‐ARs, knock‐in HA‐α 2a ‐ARs, co‐immunoprecipitation, mass spectrometry analysis, we have determined the Gb and Gg subunits that interact with α 2a ‐ARs and SNARE complexes. So far, we find Gβ2 preferentially interacting with activated auto α 2a ‐ARs. We also see a basal Gβγ‐SNARE interaction and the 2 fold enhancement of this interaction upon the auto α 2a ‐ARs activation. Further understanding Gβγ specificity and Gβγ‐SNARE interaction may offer new insights into the normal functioning of the brain, as well as better understanding of disease progression. Support or Funding Information This work was supported by the National Institutes of Health (EY10291, MH101679, DK109204, and T32)