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

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