成年神经元IIS/FOXO转录组显示成年表型调节者
Rachel Kaletsky1, Vanisha Lakhina1, Rachel Arey1
1Department of Molecular Biology &LSI Genomics, Princeton University, Princeton, New Jersey 08544, USA.
Nature
|December 18, 2015
概括
胰岛素/类似胰岛素的生长因子信号 (IIS) 通过DAF-16 (分叉盒O) 转录因子调节关键生命过程. 这项研究确定了神经元特异性的 IIS 点, 对于记忆和轴突再生至关重要.
科学领域:
- 分子生物学
- 神经科学
- 遗传学
背景情况:
- 胰岛素/类似胰岛素的生长因子信号 (IIS) 控制基本的生物过程,如生长,新陈代谢和寿命.
- DAF-16转录因子 (哺乳动物叉头盒O蛋白的同类) 调解了IIS效应,其全球点已先前确定.
- 虽然IIS和DAF-16影响神经元功能,如记忆和轴突再生,但神经元特异性点在很大程度上是未知的.
研究的目的:
- 在成年Caenorhabditis elegans中确定IIS/DAF-16通路的神经元特异性点.
- 研究神经元与非神经元 IIS/DAF-16 标在调节寿命和神经元表型方面的不同作用.
- 了解IIS/DAF-16途径如何促进与年龄相关的神经元维护和延长寿命.
主要方法:
- 用于转录造型的成年Caenorhabditis elegans神经元的分离.
- 野生类型和IIS/DAF-16突变成年神经元转录组的比较分析.
- 在神经和非神经组织中对特定转录因子 (例如,FKH-9) 的功能性评估.
主要成果:
- 确定与常规寿命和代谢目标不同的神经元特定的IIS/DAF-16目标.
- 证明这些神经元特异性点对于IIS突变体的记忆增强至关重要 (daf-2).
- 叉头转录因子FKH-9扮演着双重的角色:神经元活动对于Daf-2突变体的与年龄相关的轴突再生是必不可少的,而非神经元活动则对其延长寿命至关重要.
结论:
- 特定于神经元的IIS/DAF-16点对于维持神经元功能至关重要,包括记忆和轴突再生,独立于规范寿命路径.
- 叉头转录因子FKH-9在调节神经元维护和寿命方面表现出明显的组织特异性功能.
- 在减少胰岛素信号的情况下,神经元特异性和正规的IIS/DAF-16点的协调作用优化了神经元活动,新陈代谢和寿命.
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