| First Author | Yim YY | Year | 2021 |
| Journal | Sci Signal | Volume | 14 |
| Issue | 714 | Pages | eabc4970 |
| PubMed ID | 34932372 | Mgi Jnum | J:347348 |
| Mgi Id | MGI:7622152 | Doi | 10.1126/scisignal.abc4970 |
| Citation | Yim YY, et al. (2021) Specificities of Gbetagamma subunits for the SNARE complex before and after stimulation of alpha(2a)-adrenergic receptors. Sci Signal 14(714):eabc4970 |
| abstractText | Ligand binding to G protein-coupled receptors (GPCRs), such as the alpha(2a)-adrenergic receptor (alpha(2a)AR), results in the activation of heterotrimeric G proteins, which consist of functionally distinct Galpha subunits and Gbetagamma dimers. alpha(2a)AR-dependent inhibition of synaptic transmission regulates functions such as spontaneous locomotor activity, anesthetic sparing, and working memory enhancement and requires the soluble NSF attachment protein receptor (SNARE) complex, a Gbetagamma effector. To understand how the Gbetagamma-SNARE complex underlies the alpha(2a)AR-dependent inhibition of synaptic transmission, we examined the specificity of Gbetagamma subunits for the SNARE complex in adrenergic neurons, in which auto-alpha(2a)ARs respond to epinephrine released from these neurons, and nonadrenergic neurons, in which hetero-alpha(2a)ARs respond to epinephrine released from other neurons. We performed a quantitative, targeted multiple reaction monitoring proteomic analysis of Gbeta and Ggamma subunits bound to the SNARE complex in synaptosomes from mouse brains. In the absence of stimulation of auto-alpha(2a)ARs, Gbeta(1) and Ggamma(3) interacted with the SNARE complex. However, Gbeta(1), Gbeta(2), and Ggamma(3) were found in the complex when auto-alpha(2a)ARs were activated by epinephrine. Further understanding of the specific usage of distinct Gbetagamma subunits in vivo may provide insights into the homeostatic regulation of synaptic transmission and the mechanisms of dysfunction that occur in neurological diseases. |
