| First Author | Yim YY | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 1718 |
| PubMed ID | 30737458 | Mgi Jnum | J:275004 |
| Mgi Id | MGI:6304556 | Doi | 10.1038/s41598-018-37222-1 |
| Citation | Yim YY, et al. (2019) The in vivo specificity of synaptic Gbeta and Ggamma subunits to the alpha2a adrenergic receptor at CNS synapses. Sci Rep 9(1):1718 |
| abstractText | G proteins are major transducers of signals from G-protein coupled receptors (GPCRs). They are made up of alpha, beta, and gamma subunits, with 16 Galpha, 5 Gbeta and 12 Ggamma subunits. Though much is known about the specificity of Galpha subunits, the specificity of Gbetagammas activated by a given GPCR and that activate each effector in vivo is not known. Here, we examined the in vivo Gbetagamma specificity of presynaptic alpha2a-adrenergic receptors (alpha2aARs) in both adrenergic (auto-alpha2aARs) and non-adrenergic neurons (hetero-alpha2aARs) for the first time. With a quantitative MRM proteomic analysis of neuronal Gbeta and Ggamma subunits, and co-immunoprecipitation of tagged alpha2aARs from mouse models including transgenic FLAG-alpha2aARs and knock-in HA-alpha2aARs, we investigated the in vivo specificity of Gbeta and Ggamma subunits to auto-alpha2aARs and hetero-alpha2aARs activated with epinephrine to understand the role of Gbetagamma specificity in diverse physiological functions such as anesthetic sparing, and working memory enhancement. We detected Gbeta2, Ggamma2, Ggamma3, and Ggamma4 with activated auto alpha2aARs, whereas we found Gbeta4 and Ggamma12 preferentially interacted with activated hetero-alpha2aARs. Further understanding of in vivo Gbetagamma specificity to various GPCRs offers new insights into the multiplicity of genes for Gbeta and Ggamma, and the mechanisms underlying GPCR signaling through Gbetagamma subunits. |
