Agonist binding to the NMDA receptor drives movement of its cytoplasmic domain without ion flow
Agonist binding to the NMDA receptor drives movement of its cytoplasmic domain without ion flow
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DOI：
10.1073/pnas.1520023112
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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：
Dore, Kim;Aow, Jonathan;Malinow, Roberto
NMDA受体（R）作为一种离子通道在脑生理和病理中起着重要作用。在这里，我们研究了离子流无关的激动剂耦合到NMDAR胞质结构域（cd）。我们测量神经元中表达的NMDAR的GluN1亚基的荧光标记的胞质结构域之间的FRET。不同的神经元隔室显示不同水平的FRET，与不同的NMDARcd构象一致。激动剂结合驱动单个NMDAR内GluN1亚基之间的FRET的快速和瞬时离子流非依赖性减少。细胞内输注靶向GluN1胞质结构域的抗体在离子流不存在的情况下阻断激动剂驱动的FRET变化，支持激动剂驱动的NMDARcd运动。这些研究表明，在没有离子流的情况下，与NMDAR结合的细胞外配体可以将构象信息传递到细胞中。
The NMDA receptor (R) plays important roles in brain physiology and pathology as an ion channel. Here we examine the ion flow-independent coupling of agonist to the NMDAR cytoplasmic domain (cd). We measure FRET between fluorescently tagged cytoplasmic domains of GluN1 subunits of NMDARs expressed in neurons. Different neuronal compartments display varying levels of FRET, consistent with different NMDARcd conformations. Agonist binding drives a rapid and transient ion flow-independent reduction in FRET between GluN1 subunits within individual NMDARs. Intracellular infusion of an antibody targeting the GluN1 cytoplasmic domain blocks agonist-driven FRET changes in the absence of ion flow, supporting agonist-driven movement of the NMDARcd. These studies indicate that extracellular ligand binding to the NMDAR can transmit conformational information into the cell in the absence of ion flow.