| First Author | Chen Y | Year | 2017 |
| Journal | Neuron | Volume | 96 |
| Issue | 5 | Pages | 1070-1083.e5 |
| PubMed ID | 29154125 | Mgi Jnum | J:256042 |
| Mgi Id | MGI:6114439 | Doi | 10.1016/j.neuron.2017.10.023 |
| Citation | Chen Y, et al. (2017) Endogenous Galphaq-Coupled Neuromodulator Receptors Activate Protein Kinase A. Neuron 96(5):1070-1083.e5 |
| abstractText | Protein kinase A (PKA) integrates inputs from G-protein-coupled neuromodulator receptors to modulate synaptic and cellular function. Galphas signaling stimulates PKA activity, whereas Galphai inhibits PKA activity. Galphaq, on the other hand, signals through phospholipase C, and it remains unclear whether Galphaq-coupled receptors signal to PKA in their native context. Here, using two independent optical reporters of PKA activity in acute mouse hippocampus slices, we show that endogenous Galphaq-coupled muscarinic acetylcholine receptors activate PKA. Mechanistically, this effect is mediated by parallel signaling via either calcium or protein kinase C. Furthermore, multiple Galphaq-coupled receptors modulate phosphorylation by PKA, a classical Galphas/Galphai effector. Thus, these results highlight PKA as a biochemical integrator of three major types of GPCRs and necessitate reconsideration of classic models used to predict neuronal signaling in response to the large family of Galphaq-coupled receptors. |
