环磷酸腺苷（cAMP）依赖信号传导作为哺乳动物昼夜节律起搏器的核心组成部分。
cAMP-dependent signaling as a core component of the mammalian circadian pacemaker.
作者信息
O'Neill John S, Maywood Elizabeth S, Chesham Johanna E, Takahashi Joseph S, Hastings Michael H
机构信息
Medical Research Council (MRC) Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
出版信息
Science. 2008 May 16;320(5878):949-53. doi: 10.1126/science.1152506.
Abstract
The mammalian circadian clockwork is modeled as transcriptional and posttranslational feedback loops, whereby circadian genes are periodically suppressed by their protein products. We show that adenosine 3',5'-monophosphate (cAMP) signaling constitutes an additional, bona fide component of the oscillatory network. cAMP signaling is rhythmic and sustains the transcriptional loop of the suprachiasmatic nucleus, determining canonical pacemaker properties of amplitude, phase, and period. This role is general and is evident in peripheral mammalian tissues and cell lines, which reveals an unanticipated point of circadian regulation in mammals qualitatively different from the existing transcriptional feedback model. We propose that daily activation of cAMP signaling, driven by the transcriptional oscillator, in turn sustains progression of transcriptional rhythms. In this way, clock output constitutes an input to subsequent cycles.
摘要
哺乳动物的昼夜节律生物钟被模拟为转录和翻译后反馈环，其中昼夜节律基因会被其蛋白质产物周期性地抑制。我们发现，3',5'-环磷酸腺苷（cAMP）信号传导构成了振荡网络的另一个真正组成部分。cAMP信号传导具有节律性，并维持视交叉上核的转录环，决定了振幅、相位和周期等典型的起搏器特性。这一作用具有普遍性，在外周哺乳动物组织和细胞系中也很明显，这揭示了哺乳动物昼夜节律调节中一个意想不到的点，在性质上与现有的转录反馈模型不同。我们提出，由转录振荡器驱动的cAMP信号传导的每日激活反过来维持转录节律的进程。通过这种方式，生物钟输出构成了后续周期的输入。
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