期刊
NEURON
卷 58, 期 1, 页码 78-88出版社
CELL PRESS
DOI: 10.1016/j.neuron.2008.01.019
关键词
-
资金
- BBSRC [BB/D004357/1, BB/E022553/1] Funding Source: UKRI
- MRC [MC_U105170643] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/D004357/1, BB/E022553/1, S18856] Funding Source: researchfish
- Medical Research Council [MC_U105170643] Funding Source: researchfish
- Biotechnology and Biological Sciences Research Council [BB/E022553/1, BB/D004357/1, S18856] Funding Source: Medline
- Howard Hughes Medical Institute Funding Source: Medline
- Medical Research Council [G0900414, MC_U105170643] Funding Source: Medline
The intrinsic period of circadian clocks is their defining adaptive property. To identify the biochemical mechanisms whereby casein kinase1 (CK1) determines circadian period in mammals, we created mouse null and tau mutants of Ck1 epsilon. Circadian period lengthened in CK1 epsilon(-/-), whereas CK1 epsilon(tau/tau) shortened circadian period of behavior in vivo and suprachiasmatic nucleus firing rates in vitro, by accelerating PERIOD-dependent molecular feedback loops. CK1 epsilon(tau/tau) also accelerated molecular oscillations in peripheral tissues, revealing its global role in circadian pacemaking. CK1 epsilon(tau) acted by promoting degradation of both nuclear and cytoplasmic PERIOD, but not CRYPTOCHROME, proteins. Together, these whole-animal and biochemical studies explain how tau, as a gain-of-function mutation, acts at a specific circadian phase to promote degradation of PERIOD proteins and thereby accelerate the mammalian clockwork in brain and periphery.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据