Conformational signaling required for synaptic plasticity by the NMDA receptor complex
Conformational signaling required for synaptic plasticity by the NMDA receptor complex
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DOI：
10.1073/pnas.1520029112
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发表时间：
2015-11-24
影响因子：
11.1
通讯作者：
Malinow, Roberto
中科院分区：
文献类型：
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作者：
Aow, Jonathan;Dore, Kim;Malinow, Roberto
已知NMDA受体（NMDAR）通过传导钙离子来传递重要信息。然而，最近的一些研究表明，NMDAR的激活可以在没有离子流的情况下触发突触可塑性。配体结合是否将信息传递给介导突触可塑性的信号分子？使用福斯特共振能量转移（FRET）成像的荧光标记的蛋白质在神经元中表达，构象信号被确定内的NMDAR复合物是必不可少的下游行动。配体结合瞬时降低NMDAR胞质结构域（cd）和相关蛋白磷酸酶1（PP 1）之间的FRET，需要NMDAR cd移动，并持续降低NMDAR cd和钙/钙调蛋白依赖性蛋白激酶II（CaMK II）之间的FRET，这是一个需要PP 1活性的过程。这些研究直接监测突触可塑性所需的NMDAR复合物处激动剂驱动的构象信号传导。
The NMDA receptor (NMDAR) is known to transmit important information by conducting calcium ions. However, some recent studies suggest that activation of NMDARs can trigger synaptic plasticity in the absence of ion flow. Does ligand binding transmit information to signaling molecules that mediate synaptic plasticity? Using Forster resonance energy transfer (FRET) imaging of fluorescently tagged proteins expressed in neurons, conformational signaling is identified within the NMDAR complex that is essential for downstream actions. Ligand binding transiently reduces FRET between the NMDAR cytoplasmic domain (cd) and the associated protein phosphatase 1 (PP1), requiring NMDARcd movement, and persistently reduces FRET between the NMDARcd and calcium/calmodulin-dependent protein kinase II (CaMKII), a process requiring PP1 activity. These studies directly monitor agonist-driven conformational signaling at the NMDAR complex required for synaptic plasticity.