Predicting temporal fluctuations in an intracellular signalling pathway

Predicting temporal fluctuations in an intracellular signalling pathway
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DOI:
10.1006/jtbi.1997.0651
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发表时间:
1998-05-07
影响因子:
2
通讯作者:
Bray, D
Bray, D
中科院分区:
生物学4区
文献类型:
--
作者:
Morton-Firth, CJ;Bray, D

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我们使用了一个新开发的随机为基础的程序来预测大肠菌群的趋化信号通路中的分子数量的波动。具体而言,我们研究了CheYp分子的时间变化,CheYp是一种已知影响鞭毛马达旋转方向的细胞质蛋白。信号分子在附近的鞭毛电机表示为根据实验观察到的浓度和速率常数的概率相互作用的单个软件对象。模拟的CheYp分子被发现经历随机波动的数量约对应于确定性计算的浓度的平均值。波动的相对幅度,作为分子总数的比例,以及它们的平均持续时间,随着模拟体积的减小而增加。在对应于细菌体积的10%的模拟中,发现波动的平均持续时间为80.7 ms,这比观察到的拴系细菌的顺时针和逆时针旋转之间的交替(通常为2.6 s)短得多。因此,我们的研究结果是不符合一个简单的阈值交叉模型的电机开关。然而,它是可能的过滤CheYp波动产生的时间分布更接近所观察到的游泳行为,我们讨论了可能的影响电机旋转的控制。(C)出版社:Academic Press Limited。
We used a newly developed stochastic-based program to predict the fluctuations in numbers of molecules in a chemotactic signalling pathway of coliform bacteria. Specifically, we examined temporal changes in molecules of CheYp, a cytoplasmic protein known to influence the direction of rotation of the flagellar motor. Signalling molecules in the vicinity of a flagellar motor were represented as individual software objects interacting according to probabilities derived from experimentally-observed concentrations and rate constants. The simulated CheYp molecules were found to undergo random fluctuations in number about an average corresponding to the deterministically calculated concentration. Both the relative amplitude of the fluctuations, as a proportion of the total number of molecules, and their average duration, increased as the simulated volume was reduced. In a simulation corresponding to 10% of the volume of a bacterium, the average duration of fluctuations was found to be 80.7 ms, which is much shorter than the observed alternations between clockwise and counter clockwise rotations of tethered bacteria (typically 2.6 s). Our results are therefore not in agreement with a simple threshold-crossing model for motor switching. However, it is possible to filter the CheYp fluctuations to produce temporal distributions closer to the observed swimming behaviour and we discuss the possible implications for the control of motor rotation. (C) 1998 Academic Press Limited.