Glutamate-Induced AMPA Receptor Desensitization Increases Their Mobility and Modulates Short-Term Plasticity through Unbinding from Stargazin
Glutamate-Induced AMPA Receptor Desensitization Increases Their Mobility and Modulates Short-Term Plasticity through Unbinding from Stargazin
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DOI：
10.1016/j.neuron.2015.01.012
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发表时间：
2015-02-18
期刊：
影响因子：
16.2
通讯作者：
Choquet, Daniel
中科院分区：
文献类型：
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作者：
Constals, Audrey;Penn, Andrew C.;Choquet, Daniel
高频刺激时AMPAR电流的短期可塑性不仅依赖于突触前递质释放和突触后AMPAR从脱敏中的恢复，还依赖于AMPAR的快速扩散。突触内的AMPAR扩散如何在毫秒尺度上调节突触传递仍然是个谜。使用单分子追踪，我们发现，谷氨酸结合后，突触AMPAR扩散更快。使用AMPAR稳定在不同的构象状态的点突变和药理学，我们表明，脱敏受体结合少stargazin和不太稳定的突触比受体在开放或封闭的休息状态。当AMPAR-stargazin相互作用中的谷氨酸依赖性损失被阻止时，AMPAR迁移率介导的短期可塑性调节被废除。我们提出，从激活到脱敏状态的过渡导致AMPAR-stargazin相互作用的部分损失，增加AMPAR的流动性，并允许更快地从脱敏介导的突触抑制中恢复，而不影响突触中AMPAR的整体纳米组织。
Short-term plasticity of AMPAR currents during high-frequency stimulation depends not only on presynaptic transmitter release and postsynaptic AMPAR recovery from desensitization, but also on fast AMPAR diffusion. How AMPAR diffusion within the synapse regulates synaptic transmission on the millisecond scale remains mysterious. Using single-molecule tracking, we found that, upon glutamate binding, synaptic AMPAR diffuse faster. Using AMPAR stabilized in different conformational states by point mutations and pharmacology, we show that desensitized receptors bind less stargazin and are less stabilized at the synapse than receptors in opened or closed-resting states. AMPAR mobility-mediated regulation of short-term plasticity is abrogated when the glutamate-dependent loss in AMPAR-stargazin interaction is prevented. We propose that transition from the activated to the desensitized state leads to partial loss in AMPAR-stargazin interaction that increases AMPAR mobility and allows faster recovery from desensitization-mediated synaptic depression, without affecting the overall nano-organization of AMPAR in synapses.