Assembly, Secretory Pathway Trafficking, and Surface Delivery of Kainate Receptors Is Regulated by Neuronal Activity.
Assembly, Secretory Pathway Trafficking, and Surface Delivery of Kainate Receptors Is Regulated by Neuronal Activity.
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DOI：
10.1016/j.celrep.2017.06.001
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发表时间：
2017-06-20
期刊：
影响因子：
8.8
通讯作者：
Henley JM
中科院分区：
文献类型：
--
作者：
Evans AJ;Gurung S;Wilkinson KA;Stephens DJ;Henley JM
离子型谷氨酸受体（iGluR）的运输和功能支持兴奋性突触传递和可塑性，并形成神经元网络。它是公认的，转录，翻译，和内吞/回收的iGluR都是由神经元活动的调节，但少得多的是已知的活性依赖性iGluR运输通过分泌途径。在这里，我们使用红藻氨酸受体亚基GluK 2作为模型iGluR货物，以显示组装，早期分泌途径贩运，和表面交付的iGluR都是由神经元活动控制。我们发现，从头红藻氨酸受体的交付差异调节GluK 2 Q/R编辑，PKC磷酸化，PDZ配体相互作用的调制。这些发现表明，除了通过再循环/内吞作用对iGluRs进行短期调节和通过改变转录/翻译进行长期调节外，iGluRs通过分泌途径的运输受到严格的活性依赖性控制，以确定表面表达的iGluRs的数量和性质。KAR可以使用局部树突状分泌网络运输到突触后，它们的分泌运输是高度活性依赖性调节的TTX减少GluK 2编辑，这促进新KAR的ER输出，KAR激活通过GluK 2上的C末端PDZ配体相互作用减缓KAR运输Evans et al.显示KAR分泌途径运输是高度活性依赖性的。这种中期调节机制表明了神经元兴奋性和网络活动如何在一系列时间过程中在多个水平上进行调节。
Ionotropic glutamate receptor (iGluR) trafficking and function underpin excitatory synaptic transmission and plasticity and shape neuronal networks. It is well established that the transcription, translation, and endocytosis/recycling of iGluRs are all regulated by neuronal activity, but much less is known about the activity dependence of iGluR transport through the secretory pathway. Here, we use the kainate receptor subunit GluK2 as a model iGluR cargo to show that the assembly, early secretory pathway trafficking, and surface delivery of iGluRs are all controlled by neuronal activity. We show that the delivery of de novo kainate receptors is differentially regulated by modulation of GluK2 Q/R editing, PKC phosphorylation, and PDZ ligand interactions. These findings reveal that, in addition to short-term regulation of iGluRs by recycling/endocytosis and long-term modulation by altered transcription/translation, the trafficking of iGluRs through the secretory pathway is under tight activity-dependent control to determine the numbers and properties of surface-expressed iGluRs. KARs can use a local dendritic secretory network for trafficking to the post-synapse Their secretory trafficking is highly activity-dependently regulated TTX decreases GluK2 editing, which promotes ER export of new KARs KAR activation slows KAR traffic via C-terminal PDZ ligand interactions on GluK2 Evans et al. show that secretory pathway trafficking of KARs is highly activity-dependent. This medium-term regulatory mechanism demonstrates how neuronal excitability and network activity are regulated at multiple levels over a range of time courses.