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The specificity of Gβγ subunits regulating exocytosis through the adrenergic α 2a receptor
Author(s) -
Yim Yun Young,
Betke Katherine,
McDonald Hayes,
Gilsbach Ralf,
Chen Yunjia,
Wang Qin,
Hein Lutz,
Schey Kevin,
Hamm Heidi
Publication year - 2015
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.29.1_supplement.935.7
Subject(s) - exocytosis , g protein coupled receptor , receptor , microbiology and biotechnology , chemistry , adrenergic , neurotransmitter , munc 18 , stimulation , g protein , adrenergic receptor , neuroscience , biology , secretion , biochemistry , synaptic vesicle , membrane , vesicle
Modulation of neurotransmitter exocytosis by Gi/o‐coupled GPCRs, such as the α 2a adrenergic receptor (α 2 a ‐AR), is a universal regulatory mechanism used to avoid overstimulation and to influence circuitry. In addition to interaction with voltage‐gated calcium channels, Gβγ release through α 2 a ‐AR directly interact with SNARE protein to inhibit exocytosis. It has been shown that these regulatory mechanisms by both presynaptic α 2 a ‐AR in adrenergic (auto α 2a ‐AR) and non‐adrenergic neurons (hetero α 2 a ‐AR) can go awry in neurological disorders such as anxiety and working memory deficits. In this project, we investigate whether auto α 2a ‐AR in sympathetic neurons use the same Gβγ as hetero α 2 a ‐AR in other neuronal types. Gβγ specificity was determined by co‐IP Gβγ with α 2 a ‐AR receptors and SNARE from synaptosomes, followed by mass spectrometry. We hypothesize that specific Gβγ's interact with activated auto‐ and hetero‐α 2 a ‐ARs and inhibit exocytosis by interacting with SNARE. We have identified Gβ1, Gβ2, Gβ4, Gβ5, Gγ2, Gγ3, Gγ4, Gγ7, Gγ12, and Gγ13 which preferentially interact with the activated auto α 2 a ‐AR and SNARE. We also expect to identify Gβ or Gγ's specific for hetero α 2 a ‐AR. These studies may identify the Gβγ‐SNARE interaction as a new therapeutic target to modulate exocytosis in combination with drugs targeted to Gi/o‐coupled GPCRs. This work was supported by the National Institutes of Health (EY10291, MH101679, and T32).