哺乳动物对昼夜节律性无时无刻的要求
Jessica W Barnes1, Shelley A Tischkau, Jeffrey A Barnes
1Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
概括
哺乳动物无时无刻 (mTim) 蛋白质对于维持大脑中昼夜节律至关重要. 研究表明,mTim通过与上体核中的周期蛋白相互作用来调节分子钟表.
科学领域:
- 时间生物学 时间生物学
- 分子生物学分子生物学
- 神经科学是一个神经科学.
背景情况:
- 转录调节器Timeless (dTim) 在多虫的昼夜节律中起着关键作用.
- 它的哺乳动物对应物,哺乳动物无时无刻 (mTim) 在哺乳动物分子钟表中的功能仍然不清楚.
研究的目的:
- 研究哺乳动物 Timeless (mTim) 在上神核 (SCN) 中的作用及其对昼夜节律的贡献.
- 为了确定mTim是否在哺乳动物的昼夜时钟中作为dTim的同类.
主要方法:
- 在老鼠SCN神经元中,mTim蛋白的有条件淘汰.
- 对SCN神经元活动节奏和核心时钟元素水平的分析.
- 全长 (mTIM-fl) 和截断 (mTIM-s) 的mTim异型体的表征.
- 免疫沉试验用于评估mTIM-fl和mPER的相互作用.
主要成果:
- mTim knockdown 破坏了SCN神经元活动节奏.
- 在mTim敲击后,观察到核心时钟元素的水平发生了变化.
- 全长的mTim (mTIM-fl) 呈现了24小时的振荡,而截断的异型 (mTIM-s) 则是构成性表达的.
- mTIM-fl与哺乳动物周期 (mPER) 蛋白在振荡的SCN细胞中相关.
结论:
- 哺乳动物无时间 (mTim) 对于维持SCN中的节律性至关重要.
- mTim是哺乳动物分子钟中负反循环的关键组成部分.
- mTim是Drosophila dTim的功能同类物,突出了保存的昼夜机制.
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