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Specificity of Gβ and γ subunits to the SNARE complex both at rest and after α2aadrenergic receptor stimulation

Y. Y. Yim, W. H. McDonald, K. M. Betke, A. Kaya, K. Hyde, K. Erreger, R. Gilsbach, L. Hein, H. E. Hamm

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Abstract

Though much is known about the various physiological functions of each GPCR and the specificity of G subunits, the specificity of G{beta}{gamma} activated by a given GPCR and activating each effector in vivo is not known. Previously, we identified different G{beta} and G{gamma} subunits interacting specifically with 2a-adrenergic receptors (2aAR). In this study, we examined its in vivo specificity to the soluble NSF attachment proteins (SNARE) complex in adrenergic (auto-2aAR) and non-adrenergic (hetero-2aAR) neurons. We applied a quantitative targeted multiple reaction monitoring proteomic analysis of G{beta} and G{gamma} subunits bound to the SNARE complex, and found only a subset of G{beta} and G{gamma} bound. Without stimulation of auto-2aAR, G{beta}1 and G{gamma}3 interacted with the SNARE complex. When auto-2aAR were activated, G{beta}1, G{beta}2, and G{gamma}3 were found. Further understanding of in vivo G{beta}{gamma} specificity to its effectors provides new insights into the multiplicity of genes for G{beta} and G{gamma}. SummarySpecific G{beta}{gamma} dimers interact with the SNARE complex following presynaptic 2aAR activation in both adrenergic and non-adrenergic neurons.

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