通过神经纤维素-1和Ras/MAPK介导的Drosophila的昼夜输出
J A Williams1, H S Su, A Bernards
1Howard Hughes Medical Institute, Center for Sleep and Respiratory Neurobiology, Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
概括
神经纤维素-1 (Nf1) 基因突变通过改变Ras/MAPK信号来破坏果的昼夜节律. 这条通路通过色素分散因子 (PDF) 将时钟细胞连接到节律行为.
科学领域:
- 时间生物学 时间生物学
- 分子生物学分子生物学
- 神经遗传学 神经遗传学
背景情况:
- 控制节律行为的生理时钟输出机制仍然不太了解.
- 德洛索菲拉中神经纤维素-1 (Nf1) 基因的突变会导致昼夜运动活动节律的中断.
- 虽然核心时钟基因振荡 (周期,无时间) 在Nf1突变者中是正常的,但时钟控制的记者振荡被改变了.
研究的目的:
- 研究神经纤维素-1 (Nf1) 基因在调节昼夜节律中的作用.
- 阐明Nf1通过哪些分子途径影响昼夜输出.
- 为了确定Nf1,Ras/MAPK信号传递和色素分散因子 (PDF) 在昼夜输出中的关系.
主要方法:
- 使用Drosophila melanogaster作为一个模型生物.
- 生成并分析了Nf1无突变.
- 评估昼夜运动活动节奏.
- 测量了核心时钟基因的振荡 (周期,无时间) 和时钟控制的记者.
- 量化了线素激活蛋白激酶 (MAPK) 的活性.
- 在Ras/MAPK路径中引入了功能丧失突变.
- 进行了对素-MAPK的免疫组织化学染色.
主要成果:
- Nf1突变导致线粒激活蛋白激酶 (MAPK) 活性增加.
- Ras/MAPK路径中的功能丧失突变拯救了Nf1突变的昼夜表型,通过Ras/MAPK显示Nf1信号.
- 免疫组织化学揭示了色素分散因子 (PDF) 含有神经终端附近的色素-MAPK的昼夜振荡.
- 这些发现表明PDF信号和Ras/MAPK在昼夜输出之间存在联系.
结论:
- 神经纤维素-1 (Nf1) 基因通过Ras/MAPK通路发挥作用,以调节Drosophila的昼夜运动活动.
- Nf1信号影响昼夜钟细胞的输出,将它们与节律行为联系起来.
- 通过PDF和Ras/MAPK信号传输,Phosfo-MAPK在PDF神经终端附近的循环振荡表明了通过PDF和Ras/MAPK信号传输将时钟输出与行为合的新机制.
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