Spatial Modeling of Vesicle Transport and the Cytoskeleton: The Challenge of Hitting the Right Road
Spatial Modeling of Vesicle Transport and the Cytoskeleton: The Challenge of Hitting the Right Road
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DOI：
10.1371/journal.pone.0029645
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发表时间：
2012-01-12
期刊：
影响因子：
3.7
通讯作者：
Reuss, Matthias
中科院分区：
文献类型：
--
作者：
Klann, Michael;Koeppl, Heinz;Reuss, Matthias
膜运输机制为许多细胞蛋白质提供了运输和分选系统。我们提出了一个机械代理为基础的计算机模拟集成和测试嵌入到一个详细的模型细胞囊泡运输的假设。该方法跟踪囊泡的数量和位置。因此，由于数量少和空间方面的随机特性都得到了保留。基于Heinrich和Rapoport（2005）的模型，以多尺度方式包括控制囊泡作用的潜在分子相互作用。通过添加马达蛋白，我们可以改善SNARE的再循环过程并模拟细胞极化。我们的模型还预测，外壳分子应该有一个高营业额的隔室膜，而马达蛋白的营业额必须是缓慢的。尽管囊泡系统的整体复杂性，但底层模型的模块化结构使其易于处理。我们将我们的模型应用于受体介导的内吞作用，并显示了极化的细胞骨架结构如何导致SNARES和酵母中的Ste2p受体在质膜中的极化分布。此外，我们可以在一个模拟中耦合信号转导和膜运输步骤，这使得能够分析受体介导的内吞作用对信号传导的影响。
The membrane trafficking machinery provides a transport and sorting system for many cellular proteins. We propose a mechanistic agent-based computer simulation to integrate and test the hypothesis of vesicle transport embedded into a detailed model cell. The method tracks both the number and location of the vesicles. Thus both the stochastic properties due to the low numbers and the spatial aspects are preserved. The underlying molecular interactions that control the vesicle actions are included in a multi-scale manner based on the model of Heinrich and Rapoport (2005). By adding motor proteins we can improve the recycling process of SNAREs and model cell polarization. Our model also predicts that coat molecules should have a high turnover at the compartment membranes, while the turnover of motor proteins has to be slow. The modular structure of the underlying model keeps it tractable despite the overall complexity of the vesicle system. We apply our model to receptor-mediated endocytosis and show how a polarized cytoskeleton structure leads to polarized distributions in the plasma membrane both of SNAREs and the Ste2p receptor in yeast. In addition, we can couple signal transduction and membrane trafficking steps in one simulation, which enables analyzing the effect of receptor-mediated endocytosis on signaling.