...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >The alpha-syntrophin PH and PDZ domains scaffold acetylcholine receptors, utrophin, and neuronal nitric oxide synthase at the neuromuscular junction.
【24h】

The alpha-syntrophin PH and PDZ domains scaffold acetylcholine receptors, utrophin, and neuronal nitric oxide synthase at the neuromuscular junction.

机译：α-syntrophinPH和PDZ域在神经肌肉接头处支撑乙酰胆碱受体，促卵磷脂和神经元一氧化氮合酶。

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

At the neuromuscular junction (NMJ), the dystrophin protein complex provides a scaffold that functions to stabilize acetylcholine receptor (AChR) clusters. Syntrophin, a key component of that scaffold, is a multidomain adapter protein that links a variety of signaling proteins and ion channels to the dystrophin protein complex. Without syntrophin, utrophin and neuronal nitric oxide synthase mu (nNOSmu) fail to localize to the NMJ and the AChRs are distributed abnormally. Here we investigate the contribution of syntrophin domains to AChR distribution and to localization of utrophin and nNOSmu at the NMJ. Transgenic mice expressing alpha-syntrophin lacking portions of the first pleckstrin homology (PH) domain (DeltaPH1a or DeltaPH1b) or the entire PDZ domain (DeltaPDZ) were bred onto the alpha-syntrophin null background. As expected the DeltaPDZ transgene did not restore the NMJ localization of nNOS. The DeltaPH1a transgene did restore postsynaptic nNOS but surprisingly did not restore sarcolemmal nNOS (although sarcolemmal aquaporin-4 was restored). Mice lacking the alpha-syntrophin PDZ domain or either half of the PH1 domain were able to restore utrophin to the NMJ but did not correct the aberrant AChR distribution of the alpha-syntrophin knock-out mice. However, mice expressing both the transgenic DeltaPDZ and the transgenic DeltaPH1a constructs did restore normal AChR distribution, demonstrating that both domains are required but need not be confined within the same protein to function. We conclude that the PH1 and PDZ domains of alpha-syntrophin work in concert to facilitate the localization of AChRs and nNOS at the NMJ.
机译：在神经肌肉接头（NMJ），肌营养不良蛋白复合物提供了一个支架，该支架具有稳定乙酰胆碱受体（AChR）簇的功能。 Syntrophin是该支架的关键组件，是一种多结构域衔接蛋白，可将多种信号蛋白和离子通道与肌营养不良蛋白复合物相连。如果没有合成营养素，则营养素和神经元一氧化氮合酶mu（nNOSmu）不能定位于NMJ，并且AChRs异常分布。在这里，我们研究了促营养素结构域对AChR分布以及对UTJ和nNOSmu在NMJ的定位的贡献。将表达缺少第一个pleckstrin同源性（PH）结构域（DeltaPH1a或DeltaPH1b）或整个PDZ结构域（DeltaPDZ）的部分α-突触核蛋白的转基因小鼠繁殖到α-突触突蛋白无效背景上。正如预期的那样，DeltaPDZ转基因不能恢复nNOS的NMJ定位。 DeltaPH1a转基因的确能恢复突触后nNOS，但出乎意料的是不能恢复肌膜nNOS（尽管肌膜水通道蛋白4得以恢复）。缺乏α-突触核蛋白PDZ结构域或PH1结构域的一半的小鼠能够将卵磷脂恢复到NMJ，但不能纠正α-突触核蛋白敲除小鼠的异常AChR分布。但是，同时表达转基因DeltaPDZ和转基因DeltaPH1a构建体的小鼠确实恢复了正常的AChR分布，表明这两个域都是必需的，但不必局限于同一蛋白即可发挥功能。我们得出结论，α-突触核蛋白的PH1和PDZ域协同工作，以促进AChR和nNOS在NMJ的定位。

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