Endogenous Gαq-Coupled Neuromodulator Receptors Activate Protein Kinase A
| Autor: | Adam J. Granger, Yao Chen, Jessica L. Saulnier, Bernardo L. Sabatini, Trinh T. Tran, Alfredo Kirkwood |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Gs alpha subunit Gi alpha subunit Biology Hippocampus Article Receptors G-Protein-Coupled 03 medical and health sciences Mice Pregnancy medicine Animals Humans Calcium Signaling Phosphorylation Protein kinase A Receptor Protein Kinase C G protein-coupled receptor General Neuroscience Cyclic AMP-Dependent Protein Kinases Receptors Muscarinic Cell biology Receptors Neurotransmitter Enzyme Activation Mice Inbred C57BL 030104 developmental biology HEK293 Cells Gq alpha subunit biology.protein GTP-Binding Protein alpha Subunits Gq-G11 Female Acetylcholine medicine.drug Signal Transduction |
| Zdroj: | Neuron. 96(5) |
| ISSN: | 1097-4199 |
| Popis: | Protein kinase A (PKA) integrates inputs from G-protein-coupled neuromodulator receptors to modulate synaptic and cellular function. Gαs signaling stimulates PKA activity, whereas Gαi inhibits PKA activity. Gαq, on the other hand, signals through phospholipase C, and it remains unclear whether Gαq-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 Gαq-coupled muscarinic acetylcholine receptors activate PKA. Mechanistically, this effect is mediated by parallel signaling via either calcium or protein kinase C. Furthermore, multiple Gαq-coupled receptors modulate phosphorylation by PKA, a classical Gαs/Gαi 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 Gαq-coupled receptors. |
| Databáze: | OpenAIRE |
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