该CRTC1-SIK1通路调节了生理时钟的携带
Aarti Jagannath1, Rachel Butler1, Sofia I H Godinho1
1Nuffield Department of Clinical Neurosciences (Nuffield Laboratory of Ophthalmology), University of Oxford, Levels 5-6 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK; pRED Pharma Research and Development F. Hoffmann-La Roche, 4070 Basel, Switzerland.
Cell
|September 3, 2013
概括
盐诱导酶1 (SIK1) 通过抑制cAMP响应元素结合蛋白 (CREB) 途径来调节昼夜时钟的重置. 减少SIK1加速了时差滞后的重新训练,为昼夜节律调节提供了一个目标.
科学领域:
- 时间生物学 时间生物学
- 分子神经科学 分子神经科学
- 分子生物学分子生物学
背景情况:
- 昼夜节律由视网膜光受体与太阳日同步.
- 生物钟的光学重置涉及CREB介导的SCN中的Per基因诱导.
- 昼夜时钟的精确机制和延迟仍然不太清楚.
研究的目的:
- 为了阐明生物钟重置背后的分子机制.
- 在SCN中识别光引入通路的关键调节者.
- 研究SIK1和CRTC1在昼夜时钟动态中的作用.
主要方法:
- 在上神核 (SCN) 中对光调节的转录组的分析.
- 调查CRTC1,CREB和SIK1.1之间的相互作用.
- 利用SCN中Sik1的淘汰来评估行为阶段转移和重新训练.
主要成果:
- 确定SIK1和CRTC1是SCN时钟重置中的关键组件.
- 光刺激促进CREB的CRTC1协同激活,诱导Per1和Sik1的表达.
- 通过酸化和禁用CRTC1,SIK1对系统产生负面反,从而抑制光线的影响.
- 淘汰Sik1增强了行为阶段转移,并在模拟时差后加速重新训练.
结论:
- SIK1充当负反调节器,限制光线对昼夜时钟重置的影响.
- 这种SIK1-CRTC1-CREB通路是生理节律的速度的关键决定因素.
- 这一途径代表了调节昼夜节律障碍的潜在治疗标.
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