High-affinity kainate receptor subunits are necessary for ionotropic but not metabotropic signaling.
High-affinity kainate receptor subunits are necessary for ionotropic but not metabotropic signaling.
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高亲和力的海藻酸盐受体亚基是离子型但不是代谢性信号传导所必需的。
DOI：
10.1016/j.neuron.2009.08.010
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发表时间：
2009-09-24
期刊：
影响因子：
16.2
通讯作者：
Contractor, Anis
中科院分区：
文献类型：
--
作者：
Fernandes, Herman B.;Catches, Justin S.;Petralia, Ronald S.;Copits, Bryan A.;Xu, Jian;Russell, Theron A.;Swanson, Geoffrey T.;Contractor, Anis
红藻氨酸受体是谷氨酸受体家族的非典型成员，其能够通过离子型和代谢型途径传递信号。在五个单独的红藻氨酸受体亚基中，高亲和力亚基GluK 4（KA 1）和GluK 5（KA 2）是独特的，因为它们在重组表达系统中不形成功能性同型受体，而是与初级亚基GluK 1 -3（GluR 5 -7）联合收割机组合以形成异聚体组装体。在这里，我们通过破坏Grik 4基因位点产生了GluK 4突变小鼠。我们发现，GluK 4亚基的损失导致突触红藻氨酸受体电流显着减少。此外，在GluK 4/GluK 5双敲除小鼠中的两个高亲和力亚基的消融导致突触红藻氨酸受体的突触前和突触后离子型功能的完全丧失。主要的亚基保留在突触质膜上，但分布在远离突触后密度和突触前活动区的地方。剩余的红藻氨酸受体的性质也发生了改变，因为红藻氨酸的应用未能引起GluK 4/GluK 5敲除神经元的反应。尽管缺乏可检测的离子型突触受体，红藻氨酸受体介导的抑制慢后超极化电流（IsAHP），这是依赖于代谢途径，是完整的GluK 4/GluK 5敲除小鼠。这些结果揭示了高亲和力红藻氨酸受体亚基作为离子型红藻氨酸受体功能的强制性组分的先前未知的关键作用，并且进一步证明红藻氨酸受体参与代谢型信号传导途径并不需要它们作为离子通道的经典作用。
Kainate receptors are atypical members of the glutamate receptor family which are able to signal through both ionotropic and metabotropic pathways. Of the five individual kainate receptor subunits the high-affinity subunits, GluK4 (KA1) and GluK5 (KA2), are unique in that they do not form functional homomeric receptors in recombinant expression systems, but combine with the primary subunits GluK1-3 (GluR5-7) to form heteromeric assemblies. Here we generated a GluK4 mutant mouse by disrupting the Grik4 gene locus. We found that loss of the GluK4 subunit leads to a significant reduction in synaptic kainate receptor currents. Moreover, ablation of both high-affinity subunits in GluK4/GluK5 double knockout mice leads to a complete loss of pre- and postsynaptic ionotropic function of synaptic kainate receptors. The principal subunits remain at the synaptic plasma membrane, but are distributed away from postsynaptic densities and presynaptic active zones. There is also an alteration in the properties of the remaining kainate receptors, as kainic acid application fails to elicit responses in GluK4/GluK5 knockout neurons. Despite the lack of detectable ionotropic synaptic receptors, the kainate receptor-mediated inhibition of the slow afterhyperpolarization current (IsAHP), which is dependent on metabotropic pathways, was intact in GluK4/GluK5 knockout mice. These results uncover a previously unknown critical role for the high-affinity kainate receptor subunits as obligatory components of ionotropic kainate receptor function, and further, demonstrate that kainate receptor participation in metabotropic signaling pathways does not require their classic role as ion channels.
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通过海藻酸盐受体突触激活内在兴奋性的代谢性调节。
DOI：
10.1523/jneurosci.5356-03.2004
发表时间：
2004-05-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
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发表时间：
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影响因子：
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