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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Endocytosis and recycling of AMPA receptors lacking GluR2/3
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Endocytosis and recycling of AMPA receptors lacking GluR2/3

机译：缺乏GluR2 / 3的AMPA受体的内吞作用和再循环

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摘要

Excitatory synapses in the mammalian brain contain two types of ligand-gated ion channels: AMPA receptors (AMPARs) and NMDA receptors (NMDARs). AMPARs are responsible for generating excitatory synaptic responses, whereas NMDAR activation triggers long-lasting changes in these responses by modulating the trafficking of AMPARs toward and away from synapses. AMPARs are tetramers composed of four subunits (GluR1-GluR4), which current models suggest govern distinct AMPAR trafficking behavior during synaptic plasticity. Here, we address the roles of GluR2 and GluR3 in controlling the recycling- and activity-dependent endocytosis of AMPARs by using cultured hippocampal neurons prepared from knockout (KO) mice lacking these subunits. We find that synapses and dendritic spines form normally in cells lacking GluR2/3 and that upon NMDAR activation, GluR2/3-lacking AMPARs are endo-cytosed in a manner indistinguishable from GluR2-containing AMPARs in wild-type (WT) neurons. AMPARs lacking GluR2/3 also recycle to the plasma membrane identically to WT AMPARs. However, because of their permeability to calcium, GluR2-lacking but not WT AMPARs exhibited robust internalization throughout the dendritic tree in response to AMPA application. Dendritic endocytosis of AMPARs also was observed in GABAergic neurons, which express a high proportion of GluR2-lacking AMPARs. These results demonstrate that GluR2 and GluR3 are not required for activity-dependent endocytosis of AMPARs and suggest that the most important property of GluR2 in the context of AMPAR trafficking may be its influence on calcium permeability.
机译：哺乳动物大脑中的兴奋性突触包含两种类型的配体门控离子通道：AMPA受体（AMPAR）和NMDA受体（NMDAR）。 AMPAR负责产生兴奋性突触反应，而NMDAR激活通过调节AMPAR朝向和远离突触的运输，触发这些反应的长期变化。 AMPAR是由四个亚基（GluR1-GluR4）组成的四聚体，当前模型表明在突触可塑性期间支配着不同的AMPAR运输行为。在这里，我们通过使用从缺乏这些亚基的基因敲除（KO）小鼠制备的培养的海马神经元来解决GluR2和GluR3在控制AMPAR的循环依赖和活性依赖性内吞作用中的作用。我们发现突触和树突棘通常在缺乏GluR2 / 3的细胞中形成，并且在NMDAR激活后，缺乏GluR2 / 3的AMPAR被内吞，其方式与野生型（WT）神经元中含GluR2的AMPAR没有区别。缺少GluR2 / 3的AMPAR也可以与WT AMPAR相同地循环到质膜。然而，由于其对钙的渗透性，响应于AMPA的应用，缺乏GluR2而不是野生型AMPAR在整个树突树上均表现出强大的内在化。在GABA能神经元中也观察到AMPAR的树突状内吞作用，该神经元表达高比例的缺乏GluR2的AMPAR。这些结果表明，GluR2和GluR3对于AMPAR的活性依赖性内吞作用不是必需的，并且表明在AMPAR转运的情况下GluR2最重要的特性可能是其对钙渗透性的影响。

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