Cited by 67Receptor Mechanisms and SignalingNeuroscience and Neuropharmacology ResearchProtein Kinase Regulation and GTPase Signaling

Endogenous Gαq-coupled neuromodulator receptors activate protein kinase A

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Chen, Yao, Granger, Adam J., Tran, Trinh, Saulnier, Jessica L., Kirkwood, Alfredo, Sabatini, Bernardo L.·2017·Neuron

Abstract

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.

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Crossref · 10.1016/j.neuron.2017.10.023

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  • GABA and Ach coreleased in cortex may act in parallel on different targets to achieve a common function, such as placing cortex in a more excitable and pro-plasticity state.

    “GABA and Ach coreleased in the cortex may act in parallel on different targets to achieve a single common function, such as placing the cortex in a more excitable and pro-plasticity state by simultaneously inhibiting Sst+ interneurons with GABA while using Ach release to excite disinhibitory interneurons and activate muscarinic receptors on pyramidal cells.90,97,98,140,141”

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Authors
Chen, Y., Granger, A. J., Tran, T., Saulnier, J. L., Kirkwood, A., & Sabatini, B. L.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Johns Hopkins University (US)
Corresponding author
Sabatini, Bernardo L.
Venue
Neuron
Publisher
Elsevier BV
Published
2017-12
Volume
96
Issue
5
Pages
1070-1083.e5
ISSN
0896-6273 (ISSN-L)
OpenAlex
W2768569010
Cited by
67
References
94
Citations by year
2026: 7 · 2025: 6 · 2024: 11 · 2023: 8 · 2022: 4 · 2021: 10 · 2020: 8 · 2019: 7 · 2018: 6
FWCI
2.34
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Nancy Lurie Marks Family Foundation (6193253-02)
  • Goldenson Fund
  • NIH (R01NS046579, F32DA035543, P30NS072030)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
protein kinase A, muscarinic receptors, G protein signaling, phospholipase C, protein kinase C, calcium signaling, hippocampus, neuromodulation
MeSH terms
Animals, Enzyme Activation, Female, Hippocampus, Humans, Mice, Inbred C57BL, Phosphorylation, Pregnancy, Protein Kinase C, Receptors, Muscarinic, Signal Transduction, Cyclic AMP-Dependent Protein Kinases, Receptors, Neurotransmitter, Calcium Signaling, Receptors, G-Protein-Coupled, GTP-Binding Protein alpha Subunits, Gq-G11, Mice, HEK293 Cells

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