Auxiliary proteins promote modal gating of AMPA- and kainate-type glutamate receptors.

Auxiliary proteins promote modal gating of AMPA- and kainate-type glutamate receptors.
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辅助蛋白促进了Ampa-和Kainate型谷氨酸受体的模态门控。

DOI:
10.1111/ejn.12519
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发表时间:
2014-04
期刊:
The European journal of neuroscience
影响因子:
--
通讯作者:
Howe JR
Howe JR
中科院分区:
其他
文献类型:
--
作者:
Zhang W;Devi SP;Tomita S;Howe JR

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α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)和红藻氨酸受体的门控行为分别通过与辅助蛋白(跨膜AMPA受体调节蛋白(TARP)和神经纤毛蛋白tolloid-like(Netos))的结合来调节。虽然AMPA和红藻氨酸受体的受体调节机制不同,与这些辅助亚基的关联导致在快速应用饱和浓度的谷氨酸的集合响应的衰减中出现缓慢的组件。我们在这里表明,这些组件产生不同的门控行为,其特征在于显着更高的开放概率(Popen),我们只观察到当核心亚基与各自的辅助合作伙伴。我们将这些行为称为门控模式,因为个体受体在秒的时间尺度上在低和高Popen门控之间切换。在任何给定的时间,AMPA和红藻氨酸受体与其辅助亚基的关联导致异质受体群体,其中一些处于高Popen模式,而另一些则显示出与单独由核心亚基形成的受体相似的门控行为。虽然模式之间的切换是不必要的,但显示两种类型门控的受体的存在对类似于在突触处看到的那些的能感电流的动力学和振幅两者具有很大的影响。
The gating behavior of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors is modulated by association with the auxiliary proteins: transmembrane AMPA receptor regulatory proteins (TARPs) and neuropilin tolloid-like (Netos), respectively. Although the mechanisms underlying receptor modulation differ for both AMPA and kainate receptors, association with these auxiliary subunits results in the appearance of a slow component in the decay of ensemble responses to rapid applications of saturating concentrations of glutamate. We show here that these components arise from distinct gating behaviors, characterized by substantially higher open probability (Popen), which we only observe when core subunits are associated with their respective auxiliary partners. We refer to these behaviors as gating modes, because individual receptors switch between the low- and high-Popen gating on a time-scale of seconds. At any given time, association of AMPA and kainate receptors with their auxiliary subunits results in a heterogeneous receptor population, some of which are in the high-Popen mode and others that display gating behavior similar to that seen for receptors formed from core subunits alone. While the switching between modes is infre quent, the presence of receptors displaying both types of gating has a large impact on both the kinetics and amplitude of ensem ble currents similar to those seen at synapses.
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