Endogenous Gαq-Coupled Neuromodulator Receptors Activate Protein Kinase A.,Neuron

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Endogenous Gαq-Coupled Neuromodulator Receptors Activate Protein Kinase A.
Neuron ( IF 14.7 ) Pub Date : 2017-Dec-06 , DOI: 10.1016/j.neuron.2017.10.023
Yao Chen ₁ , Adam J Granger ₁ , Trinh Tran ₂ , Jessica L Saulnier ₁ , Alfredo Kirkwood ₂ , Bernardo L Sabatini ₁

Affiliation

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.

中文翻译：

内源性 Gαq 偶联神经调节剂受体激活蛋白激酶 A。

蛋白激酶 A (PKA) 整合来自 G 蛋白偶联神经调节剂受体的输入来调节突触和细胞功能。Gαs 信号刺激 PKA 活性，而 Gαi 抑制 PKA 活性。另一方面，Gαq 通过磷脂酶 C 发出信号，目前尚不清楚 Gαq 偶联受体是否在其天然环境中向 PKA 发出信号。在这里，使用急性小鼠海马切片中 PKA 活性的两个独立光学报告器，我们显示内源性 Gαq 偶联毒蕈碱乙酰胆碱受体激活 PKA。从机制上讲，这种效应是通过钙或蛋白激酶 C 的平行信号传导介导的。此外，多个 Gαq 偶联受体通过 PKA（一种经典的 Gαs/Gαi 效应器）调节磷酸化。因此，

更新日期：2017-11-19

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