Endogenous Gαq-coupled neuromodulator receptors activate protein kinase A
Open accessAbstract
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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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”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [141]
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Self-citation
- 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)
- PMC
- PMC5726796
- 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
- bronze
- doi.org
- Licence
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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