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Endogenous G?q-Coupled Neuromodulator Receptors Activate Protein Kinase A.

ABSTRACT: Protein kinase A (PKA) integrates inputs from G-protein-coupled neuromodulator receptors to modulate synaptic and cellular function. G?s signaling stimulates PKA activity, whereas G?i inhibits PKA activity. G?q, on the other hand, signals through phospholipase C, and it remains unclear whether G?q-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 G?q-coupled muscarinic acetylcholine receptors activate PKA. Mechanistically, this effect is mediated by parallel signaling via either calcium or protein kinase C. Furthermore, multiple G?q-coupled receptors modulate phosphorylation by PKA, a classical G?s/G?i 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 G?q-coupled receptors.

SUBMITTER: Chen Y

PROVIDER: S-EPMC5726796 | biostudies-other | 2017 Dec

REPOSITORIES: biostudies-other

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Endogenous Gαq-Coupled Neuromodulator Receptors Activate Protein Kinase A.

Chen Yao Y Granger Adam J AJ Tran Trinh T Saulnier Jessica L JL Kirkwood Alfredo A Sabatini Bernardo L BL

Neuron 20171116 5

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 ...[more]

PMID: 29154125

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