Ho Po-Yi, Martins Bruno M C, Amir Ariel
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts.
Sainsbury Laboratory, University of Cambridge, Cambridge, United Kingdom.
Biophys J. 2020 Jun 16;118(12):2905-2913. doi: 10.1016/j.bpj.2020.04.038. Epub 2020 May 20.
The cyanobacterium Synechococcus elongatus possesses a circadian clock in the form of a group of proteins whose concentrations and phosphorylation states oscillate with daily periodicity under constant conditions. The circadian clock regulates the cell cycle such that the timing of the cell divisions is biased toward certain times during the circadian period, but the mechanism underlying this phenomenon remains unclear. Here, we propose a mechanism in which a protein limiting for division accumulates at a rate proportional to the cell volume growth and is modulated by the clock. This "modulated rate" model, in which the clock signal is integrated over time to affect division timing, differs fundamentally from the previously proposed "gating" concept, in which the clock is assumed to suppress divisions during a specific time window. We found that although both models can capture the single-cell statistics of division timing in S. elongatus, only the modulated rate model robustly places divisions away from darkness during changes in the environment. Moreover, within the framework of the modulated rate model, existing experiments on S. elongatus are consistent with the simple mechanism that division timing is regulated by the accumulation of a division limiting protein in a phase with genes whose activity peaks at dusk.
蓝藻聚球藻拥有一组蛋白质形式的生物钟，在恒定条件下，这些蛋白质的浓度和磷酸化状态会以每日周期性振荡。生物钟调节细胞周期，使得细胞分裂的时间在昼夜周期中偏向某些特定时间，但这种现象背后的机制仍不清楚。在此，我们提出一种机制，即一种限制分裂的蛋白质以与细胞体积增长成比例的速率积累，并受生物钟调节。这种“调节速率”模型，其中生物钟信号随时间整合以影响分裂时间，与先前提出的“门控”概念根本不同，在“门控”概念中，生物钟被认为在特定时间窗口内抑制分裂。我们发现，虽然这两种模型都能捕捉聚球藻分裂时间的单细胞统计数据，但只有调节速率模型能在环境变化期间有力地使分裂远离黑暗。此外，在调节速率模型的框架内，现有的关于聚球藻的实验与这样一种简单机制一致，即分裂时间由一种限制分裂的蛋白质在与黄昏时活性达到峰值的基因同一阶段的积累来调节。
