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Endogenous Gαq-Coupled Neuromodulator Receptors Activate Protein Kinase A.

Neuron. 2017; 
Chen Y, Granger AJ, Tran T, Saulnier JL, Kirkwood A, Sabatini BL.
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摘要

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 P... More

关键词

G protein-coupled receptor; Gαq signaling; acetylcholine; designer receptors; fluorescence lifetime imaging microscopy; hippocampus; muscarinic receptors; neuromodulation; optical reporters; protein kinase A