Computational modelling suggests dynamic interactions between Ca2+, IP3 and G protein-coupled modules are key to robust Dictyostelium aggregation.

Computational modelling suggests dynamic interactions between Ca2+, IP3 and G protein-coupled modules are key to robust Dictyostelium aggregation.
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计算模型表明 Ca2、IP3 和 G 蛋白偶联模块之间的动态相互作用是盘基网柄菌稳健聚集的关键。

DOI:
10.1039/b822074c
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发表时间:
2009
影响因子:
--
通讯作者:
Valeyev NV
Valeyev NV
中科院分区:
生物3区
文献类型:
--
作者:
Valeyev NV

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在饥饿条件下,网骨藻细胞开始一个发育程序,在此期间,它们通过趋化性聚集以形成多细胞结构,所述趋化性由在细胞与细胞之间稳健地传递的环AMP的传播波引导。在本文中,我们开发和分析了一个新的模型的细胞内和细胞外arcAMP依赖的过程,调节Dictyosteoblasts迁移。该模型允许,第一次,钙,IP3和G蛋白依赖性模块之间的动态相互作用的定量分析被证明是关键的产生强大的cAMP振荡在Dictyosteoblasts细胞。该模型提供了一个机制的解释,在最近的实验中看到的钙调蛋白抑制剂calmidazolium(R24571)的应用到Dictyosteoprotein细胞胞质游离钙离子浓度的瞬时增加,也允许阐明的影响,改变拉伸激活通道的电导率和外部磷酸二酯酶的浓度对振荡制度的一个单独的细胞。新模型的鲁棒性的严格分析表明,不同模块之间的相互作用显着降低了所得的cAMP振荡的灵敏度,在不同的Dictyosteoprotein细胞的动力学变化,空间和时间同步的chemoattractive cAMP波的产生,引导Dictyosteoprotein聚集的基本要求。
Under conditions of starvation, Dictyostelium cells begin a programme of development during which they aggregate to form a multicellular structure by chemotaxis, guided by propagating waves of cyclic AMP that are relayed robustly from cell to cell. In this paper, we develop and analyse a new model for the intracellular and extracellularcAMP dependent processes that regulate Dictyostelium migration. The model allows, for the first time, a quantitative analysis of the dynamic interactions between calcium, IP3 and G protein-dependent modules that are shown to be key to the generation of robust cAMP oscillations in Dictyostelium cells. The model provides a mechanistic explanation for the transient increase in cytosolic free Ca2+ concentration seen in recent experiments with the application of the calmodulin inhibitor calmidazolium (R24571) to Dictyostelium cells, and also allows elucidation of the effects of varying both the conductivity of stretch-activated channels and the concentration of external phosphodiesterase on the oscillatory regime of an individual cell. A rigorous analysis of the robustness of the new model shows that interactions between the different modules significantly reduce the sensitivity of the resulting cAMP oscillations to variations in the kinetics of different Dictyostelium cells, an essential requirement for the generation of the spatially and temporally synchronised chemoattractantcAMP waves that guide Dictyostelium aggregation.
G 蛋白和 Ca2 通路之间的串扰会改变细胞内 cAMP 水平。
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发表时间: 2009
影响因子: --
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