Subunit interaction with PICK and GRIP controls Ca2+ permeability of AMPARs at cerebellar synapses
Subunit interaction with PICK and GRIP controls Ca2+ permeability of AMPARs at cerebellar synapses
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DOI：
10.1038/nn1468
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发表时间：
2005-06-01
影响因子：
25
通讯作者：
Cull-Candy, SG
中科院分区：
文献类型：
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作者：
Liu, SQJ;Cull-Candy, SG
在许多兴奋性中枢突触，活动通过修饰突触后AMPA受体（AMPAR）产生突触反应的持久变化。虽然很多是已知的蛋白质参与的Ca 2+不渗透（含GluR 2）AMPAR的运输，很少有人知道的蛋白质合作伙伴，调节亚基运输和可塑性的Ca 2+渗透（GluR 2缺乏）AMPAR。在小脑平行纤维-星状细胞突触中，活动触发了一种新型的可塑性：通过GluR 2缺乏的突触AMPAR的Ca 2+内流驱动含GluR 2的AMPAR的掺入，产生兴奋性突触后电流特性的快速，持久的变化。在这里，我们研究如何谷氨酸受体相互作用蛋白（GRIP，也称为AMPAR结合蛋白或ABP）和蛋白质与C-激酶1（PICK）相互作用调节亚基运输和可塑性。我们发现，重复的突触活动触发突触GluR 2缺乏AMPAR的损失，通过选择性地破坏它们与GRIP的相互作用，PICK驱动含GluR 2受体的活性依赖性传递。AMPAR的这种动态调节为控制突触受体的Ca 2+渗透性提供了反馈机制。
At many excitatory central synapses, activity produces a lasting change in the synaptic response by modifying postsynaptic AMPA receptors (AMPARs). Although much is known about proteins involved in the trafficking of Ca2+-impermeable (GluR2-containing) AMPARs, little is known about protein partners that regulate subunit trafficking and plasticity of Ca2+-permeable (GluR2-lacking) AMPARs. At cerebellar parallel fiber - stellate cell synapses, activity triggers a novel type of plasticity: Ca2+ influx through GluR2-lacking synaptic AMPARs drives incorporation of GluR2-containing AMPARs, generating rapid, lasting changes in excitatory postsynaptic current properties. Here we examine how glutamate receptor interacting protein ( GRIP, also known as AMPAR binding protein or ABP) and protein interacting with C-kinase-1 ( PICK) regulate subunit trafficking and plasticity. We find that repetitive synaptic activity triggers loss of synaptic GluR2-lacking AMPARs by selectively disrupting their interaction with GRIP and that PICK drives activity-dependent delivery of GluR2-containing receptors. This dynamic regulation of AMPARs provides a feedback mechanism for controlling Ca2+ permeability of synaptic receptors.