...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The European Journal of Neuroscience >The delta subfamily of glutamate receptors: Characterization of receptor chimeras and mutants
【24h】

The delta subfamily of glutamate receptors: Characterization of receptor chimeras and mutants

机译：谷氨酸受体的δ亚家族：受体嵌合体和突变体的表征

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The delta receptors, GluD1 and GluD2, are regarded as a subfamily of the ionotropic glutamate receptors solely because of sequence homology. While they play important roles in cerebellar function and high-frequency hearing and appear to serve structural functions at synapses, ligand-gated ion channel function has not been observed. However, we have previously shown that GluD2 can form functional ion channels when grafted with the ligand binding domain of a kainate receptor. In this study, we characterized this chimera as well as additional rat delta receptor chimeras and point mutants in more detail. We found that the kainate receptor ligand binding domain renders GluD1 functional as well, and GluD2 becomes a functional ion channel also when provided with an AMPA receptor ligand binding domain. Point mutations indicate that the GluD2 ion pore operates similarly but not identically to that of AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and kainate receptors. GluD2 mutated at a conserved arginine within the linker region connecting the ligand binding domain to the ion pore domain displays spontaneous currents that occur in the absence of agonists and are inhibited by agonist application - a behavior reminiscent of that of the previously characterized lurcher mutant. Using our chimeric approach, we provide evidence that this inhibition of spontaneous currents by agonists may be caused by desensitization. Our results show that delta receptors have functional gating machineries and ion permeation pathways similar but not identical to those of AMPA and kainate receptors, while the key differences seem to be located within the ligand binding domain.
机译：仅由于序列同源性，δ受体GluD1和GluD2被认为是离子型谷氨酸受体的亚家族。尽管它们在小脑功能和高频听力中起着重要作用，并且似乎在突触中起结构功能的作用，但尚未观察到配体门控离子通道功能。但是，我们先前已经表明，当将GluD2嫁接到海藻酸盐受体的配体结合域时，可以形成功能性离子通道。在这项研究中，我们更详细地描述了这种嵌合体以及其他大鼠δ受体嵌合体和点突变体的特征。我们发现，海藻酸盐受体配体结合结构域也使GluD1发挥功能，而当提供AMPA受体配体结合结构域时，GluD2也成为功能性离子通道。点突变表明GluD2离子孔的运作与AMPA（α-氨基-3-羟基-5-甲基异恶唑-4-丙酸）和海藻酸盐受体相似，但不完全相同。在将配体结合结构域与离子孔结构域连接的连接子区域内的保守精氨酸处突变的GluD2显示自发电流，该电流在不存在激动剂的情况下会发生，并受到激动剂的施加抑制-这种行为让人联想到先前表征的lurcher突变体。使用我们的嵌合方法，我们提供证据表明激动剂对自发电流的抑制可能是脱敏引起的。我们的结果表明，δ受体的功能门控机制和离子渗透途径与AMPA和kainate受体相似，但不完全相同，但主要区别似乎位于配体结合域内。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号