Stochastic control of spontaneous signal generation for gradient sensing in chemotaxis
Stochastic control of spontaneous signal generation for gradient sensing in chemotaxis
复制标题
DOI：
10.1016/j.jtbi.2008.08.012
复制
发表时间：
2008-11-21
影响因子：
2
通讯作者：
Ishi, Shin
中科院分区：
文献类型：
--
作者：
Naoki, Honda;Sakumura, Yuichi;Ishi, Shin
趋化性的特征是自发的细胞行为。这种自发性的结果，部分，从细胞内反应的随机性。趋化细胞的自发和随机迁移受自发产生的信号调节，即磷酸肌醇-3，4，5-三磷酸水平的短暂局部增加（PIP 3脉冲）。在这项研究中，我们试图阐明产生这些PIP 3脉冲的机制，以及这些脉冲如何有助于趋化过程中的梯度感应。为此，我们构建了一个简单的生物物理模型的细胞内信号转导组成的肌醇磷脂信号通路和小GTP酶。我们的理论分析表明，模型的非线性动力学可以产生可激发系统，并且随机反应允许系统自发地被激发，这与PIP 3脉冲相对应。基于这些结果。我们构建了梯度感应的假设;化学梯度在空间上改变了激发的势垒，然后PIP 3脉冲优先在暴露于较高化学浓度的细胞一侧产生。然后，我们验证了我们的假设，使用随机模拟的信号转导。(C)2008爱思唯尔有限公司保留所有权利。
Chemotaxis is characterized by spontaneous cellular behavior. This spontaneity results, in part, from the stochasticity of intracellular reactions. Spontaneous and random migration of chemotactic cells is regulated by spontaneously generated signals, namely transient local increases in the level of phosphoinositol-3,4,5-triphosphate (PIP3 pulses). In this study, we attempted to elucidate the mechanisms that generate these PIP3 pulses and how the pulses contribute to gradient sensing during chemotaxis. To this end, we constructed a simple biophysical model of intracellular signal transduction consisting of an inositol phospholipid signaling pathway and small GTPases. Our theoretical analysis revealed that an excitable system can emerge from the non-linear dynamics of the model and that, stochastic reactions allow the system to spontaneously become excited, which was corresponded to the PIP3 pulses. Based on these results. we framed a hypothesis of the gradient sensing; a chemical gradient spatially modifies a potential barrier for excitation and then PIP3 pulses are preferentially generated on the side of the cell exposed to the higher chemical concentration. We then validated our hypothesis using stochastic simulations of the signal transduction. (C) 2008 Elsevier Ltd. All rights reserved.