A model for the Neurospora circadian clock
A model for the Neurospora circadian clock
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DOI：
10.1529/biophysj.104.053975
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发表时间：
2005-04-01
影响因子：
3.4
通讯作者：
François, P
中科院分区：
文献类型：
--
作者：
François, P
生物钟是重要的生物振荡器，通常涉及两个反馈回路。在这里，我们提出了一个新的模型来研究粗糙脉孢菌的昼夜节律时钟。首先，我们对其主要的负反馈回路进行了建模，包括仅有实验证明的反应、白领复合体(WCC)对频率的转录激活(FRQ)，以及FRQ与WCC的转录后二聚。这个主循环足以产生振荡，而且几乎所有已知的昼夜节律时钟的核心都有一个类似的循环。其次，对模型进行了改进，以包括FRQ(正第二反馈环)对白领1(WC-1)蛋白质合成的不太典型的促进作用。通过对不同假设的数值检验，我们提出了WC-1的合成受到FRQ单体的促进和FRQ二聚体的抑制。我们证明了这第二个回路对振子周期对参数变化的稳健性有很大贡献。对光脉冲的相位响应曲线也进行了计算，与实验结果吻合较好。在一般水平上，我们的结果表明，显式时间延迟不是持续振荡所必需的，但考虑到mRNA动力学和蛋白质-蛋白质相互作用是至关重要的。
Circadian clocks are important biological oscillators that generally involve two feedback loops. Here, we propose a new model for the Neurospora crassa circadian clock. First, we model its main negative feedback loop, including only experimentally well-documented reactions, the transcriptional activation of frequency (frq) by the white-collar complex (WCC), and the post-transcriptional dimerization of FRQ with WCC. This main loop is sufficient for oscillations and a similar one lies at the core of almost all known circadian clocks. Second, the model is refined to include the less characterized enhancement of white-collar 1 (WC-1) protein synthesis by FRQ, the positive second feedback loop. Numerical testing of different hypotheses led us to propose that the synthesis of WC-1 is enhanced by FRQ monomers and repressed by FRQ dimers. We demonstrate that this second loop contributes significantly to the robustness of the oscillator period against parameter variation. A phase response curve to light pulses is also computed and agrees well with experiments. On a general level, our results show that explicit time delays are not required for sustained oscillations but that it is crucial to take into account mRNA dynamics and protein-protein interactions.