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空间限制的细胞内信号建模。

Modeling of spatially-restricted intracellular signaling.

机构信息

Department of Pharmacology and System Therapeutics, Friedman Brain Institute, Systems Biology Center of New York, Mount Sinai School of Medicine, New York, NY, USA.

出版信息

Wiley Interdiscip Rev Syst Biol Med. 2012 Jan-Feb;4(1):103-15. doi: 10.1002/wsbm.155. Epub 2011 Jul 15.

DOI:10.1002/wsbm.155
PMID:21766466
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4108591/
Abstract

Understanding the signaling capabilities of a cell presents a major challenge, not only due to the number of molecules involved, but also because of the complex network connectivity of intracellular signaling. Recently, the proliferation of quantitative imaging techniques has led to the discovery of the vast spatial organization of intracellular signaling. Computational modeling has emerged as a powerful tool for understanding how inhomogeneous signaling originates and is maintained. This article covers the current imaging techniques used to obtain quantitative spatial data and the mathematical approaches used to model spatial cell biology. Modeling-derived hypotheses have been experimentally tested and the integration of modeling and imaging approaches has led to non-intuitive mechanistic insights.

摘要

理解细胞的信号转导功能是一个重大挑战,不仅因为涉及的分子数量众多,还因为细胞内信号转导的复杂网络连接。最近,定量成像技术的激增使得人们发现了细胞内信号转导的巨大空间组织。计算建模已成为理解不均匀信号起源和维持的强大工具。本文涵盖了用于获取定量空间数据的当前成像技术以及用于对空间细胞生物学进行建模的数学方法。通过实验测试了基于模型的假说,并且建模和成像方法的整合带来了非直观的机械洞察力。

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本文引用的文献

1
Signaling diversity of PKA achieved via a Ca2+-cAMP-PKA oscillatory circuit.通过 Ca2+-cAMP-PKA 振荡回路实现的 PKA 的信号多样性。
Nat Chem Biol. 2011 Jan;7(1):34-40. doi: 10.1038/nchembio.478. Epub 2010 Nov 21.
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Regulation of Ras localization by acylation enables a mode of intracellular signal propagation.酰化调节 Ras 定位从而实现细胞内信号传播的模式。
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Models at the single cell level.单细胞水平模型。
Wiley Interdiscip Rev Syst Biol Med. 2010 Jan-Feb;2(1):34-48. doi: 10.1002/wsbm.49.
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Regression analysis for constraining free parameters in electrophysiological models of cardiac cells.回归分析在心脏细胞电生理模型自由参数约束中的应用。
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Classic and contemporary approaches to modeling biochemical reactions.经典和现代的生化反应建模方法。
Genes Dev. 2010 Sep 1;24(17):1861-75. doi: 10.1101/gad.1945410.
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The role of type 4 phosphodiesterases in generating microdomains of cAMP: large scale stochastic simulations.4 型磷酸二酯酶在生成 cAMP 微区中的作用:大规模随机模拟。
PLoS One. 2010 Jul 22;5(7):e11725. doi: 10.1371/journal.pone.0011725.
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Type 4 phosphodiesterase plays different integrating roles in different cellular domains in pyramidal cortical neurons.4 型磷酸二酯酶在皮质锥体神经元的不同细胞域中发挥不同的整合作用。
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Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5459-64. doi: 10.1073/pnas.0909671107. Epub 2010 Mar 8.
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Visualization of DNA methylation and histone modifications in living cells.活细胞内 DNA 甲基化和组蛋白修饰的可视化。
Curr Opin Cell Biol. 2010 Jun;22(3):412-8. doi: 10.1016/j.ceb.2010.02.004. Epub 2010 Mar 6.
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Self-organization of intracellular gradients during mitosis.有丝分裂过程中细胞内梯度的自组织。
Cell Div. 2010 Jan 29;5(1):5. doi: 10.1186/1747-1028-5-5.