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

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

2020-05-01 biochemistry
10.1101/2020.04.29.065136 bioRxiv
Show 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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