通过 Src 家族激酶对 GluN2A 与 GluN2B 受体的差异化调节实现型变协同作用。
Metaplasticity gated through differential regulation of GluN2A versus GluN2B receptors by Src family kinases.
机构信息
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
出版信息
EMBO J. 2012 Feb 15;31(4):805-16. doi: 10.1038/emboj.2011.453. Epub 2011 Dec 20.
Abstract
Metaplasticity is a higher form of synaptic plasticity that is essential for learning and memory, but its molecular mechanisms remain poorly understood. Here, we report that metaplasticity of transmission at CA1 synapses in the hippocampus is mediated by Src family kinase regulation of NMDA receptors (NMDARs). We found that stimulation of G-protein-coupled receptors (GPCRs) regulated the absolute contribution of GluN2A-versus GluN2B-containing NMDARs in CA1 neurons: pituitary adenylate cyclase activating peptide 1 receptors (PAC1Rs) selectively recruited Src kinase, phosphorylated GluN2ARs, and enhanced their functional contribution; dopamine 1 receptors (D1Rs) selectively stimulated Fyn kinase, phosphorylated GluN2BRs, and enhanced these currents. Surprisingly, PAC1R lowered the threshold for long-term potentiation while long-term depression was enhanced by D1R. We conclude that metaplasticity is gated by the activity of GPCRs, which selectively target subtypes of NMDARs via Src kinases.
摘要
代谢型可塑性是一种更高形式的突触可塑性，对于学习和记忆至关重要，但它的分子机制仍知之甚少。在这里，我们报告海马 CA1 突触传递的代谢型可塑性是由 Src 家族激酶调节 NMDA 受体（NMDAR）介导的。我们发现，G 蛋白偶联受体（GPCR）的刺激调节了 CA1 神经元中 GluN2A-与 GluN2B 包含的 NMDAR 的绝对贡献：垂体腺苷酸环化酶激活肽 1 受体（PAC1Rs）选择性募集 Src 激酶，磷酸化 GluN2ARs，并增强其功能贡献；多巴胺 1 受体（D1Rs）选择性地刺激 Fyn 激酶，磷酸化 GluN2BRs，并增强这些电流。令人惊讶的是，PAC1R 降低了长时程增强的阈值，而 D1R 增强了长时程抑制。我们得出结论，代谢型可塑性由 GPCR 的活性控制，GPCR 通过 Src 激酶选择性靶向 NMDAR 的亚型。
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