...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Control Of Extracellular Cleavage Of Probdnf By High Frequency Neuronal Activity
【24h】

Control Of Extracellular Cleavage Of Probdnf By High Frequency Neuronal Activity

机译：高频神经元活动控制probdnf的胞外切割。

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

Pro- and mature neurotrophins often elicit opposing biological effects. For example, mature brain-derived neurotrophic factor (mBDNF) is critical for long-term potentiation induced by high-frequency stimulation, whereas proBDNF facilitate long-term depression induced by low-frequency stimulation. Because mBDNF is derived from proBDNF by endoproteolytic cleavage, mechanisms regulating the cleavage of proBDNF may control the direction of BDNF regulation. Using methods that selectively detect proBDNF or mBDNF, we show that low-frequency stimulation induced predominant proBDNF secretion in cultured hippocampal neurons. In contrast, high-frequency stimulation preferentially increased extracellular mBDNF. Inhibition of extracellular, but not intracellular cleavage of proBDNF greatly reduced high-frequency stimulation-induced extracellular mBDNF. Moreover, high-frequency, but not low-frequency stimulation selectively induced the secretion of tissue plasminogen activator, a key protease involved in extracellular proBDNF to mBDNF conversion. Thus, high-frequency neuronal activity controls the ratio of extracellular proBDNF/mBDNF by regulating the secretion of extracellular proteases. Our study demonstrates activity-dependent control of extracellular proteolytic cleavage of a secretory protein, and reveals an important mechanism that controls diametrically opposed functions of BDNF isoforms.
机译：前和成熟的神经营养蛋白通常会引起相反的生物学效应。例如，成熟的脑源性神经营养因子（mBDNF）对于高频刺激诱发的长期增强至关重要，而proBDNF则有助于低频刺激诱发的长期抑郁。由于mBDNF是通过内蛋白水解切割从proBDNF衍生而来的，因此调节proBDNF切割的机制可能会控制BDNF调节的方向。使用选择性检测proBDNF或mBDNF的方法，我们显示低频刺激诱导培养的海马神经元中主要的proBDNF分泌。相反，高频刺激优先增加细胞外mBDNF。抑制proBDNF的细胞外裂解，但不能抑制细胞内裂解，大大降低了高频刺激诱导的细胞外mBDNF。此外，高频刺激而不是低频刺激选择性地诱导组织纤溶酶原激活物的分泌，纤溶酶原激活物是细胞外proBDNF转化为mBDNF的关键蛋白酶。因此，高频神经元活性通过调节细胞外蛋白酶的分泌来控制细胞外proBDNF / mBDNF的比例。我们的研究表明分泌蛋白的细胞外蛋白水解裂解的活性依赖控制，并揭示了控制截然相反的BDNF亚型功能的重要机制。

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