The in vivo specificity of synaptic G? and G? subunits to the ?2a adrenergic receptor at CNS synapses.

ABSTRACT: G proteins are major transducers of signals from G-protein coupled receptors (GPCRs). They are made up of ?, ?, and ? subunits, with 16?G?, 5?G? and 12?G? subunits. Though much is known about the specificity of G? subunits, the specificity of G??s activated by a given GPCR and that activate each effector in vivo is not known. Here, we examined the in vivo G?? specificity of presynaptic ?2a-adrenergic receptors (?2aARs) in both adrenergic (auto-?2aARs) and non-adrenergic neurons (hetero-?2aARs) for the first time. With a quantitative MRM proteomic analysis of neuronal G? and G? subunits, and co-immunoprecipitation of tagged ?2aARs from mouse models including transgenic FLAG-?2aARs and knock-in HA-?2aARs, we investigated the in vivo specificity of G? and G? subunits to auto-?2aARs and hetero-?2aARs activated with epinephrine to understand the role of G?? specificity in diverse physiological functions such as anesthetic sparing, and working memory enhancement. We detected G?2, G?2, G?3, and G?4 with activated auto ?2aARs, whereas we found G?4 and G?12 preferentially interacted with activated hetero-?2aARs. Further understanding of in vivo G?? specificity to various GPCRs offers new insights into the multiplicity of genes for G? and G?, and the mechanisms underlying GPCR signaling through G?? subunits.

SUBMITTER: Yim YY 

PROVIDER: S-EPMC6368627 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature