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非洲爪蟾卵母细胞中丝裂原活化蛋白激酶(MAPK)级联反应的信号传播:双稳性和超敏感性在一个混合问题中的作用

Signal propagation of the MAPK cascade in Xenopus oocytes: role of bistability and ultrasensitivity for a mixed problem.

作者信息

Blossey Ralf, Bodart Jean-François, Devys Anne, Goudon Thierry, Lafitte Pauline

机构信息

Institut de Recherche Interdisciplinaire, CNRS USR 3078, Parc de la Haute Borne, 50 avenue de Halley, BP 70478, 59658 Villeneuve d'Ascq Cedex, France.

出版信息

J Math Biol. 2012 Jan;64(1-2):1-39. doi: 10.1007/s00285-011-0403-y. Epub 2011 Feb 3.

Abstract

The MAPK signaling cascade is nowadays understood as a network module highly conserved across species. Its main function is to transfer a signal arriving at the plasma membrane to the cellular interior. Current understanding of 'how' this is achieved involves the notions of ultrasensitivity and bistability which relate to the nonlinear dynamics of the biochemical network, ignoring spatial aspects. Much less, indeed, is so far known about the propagation of the signal through the cytoplasm. In this work we formulate, starting from a Michaelis-Menten model for the MAPK cascade in Xenopus oocytes, a reaction-diffusion model of the cascade. We study this model in one space dimension. Basing ourselves on previous general results on reaction diffusion models, we particularly study for our model the conditions for signal propagation. We show that the existence of a propagating front depends sensitively on the initial and boundary conditions at the plasma membrane. Possible biological consequences of this finding are discussed.

摘要

如今,丝裂原活化蛋白激酶(MAPK)信号级联被认为是一个在物种间高度保守的网络模块。其主要功能是将到达质膜的信号传递到细胞内部。目前对于“如何”实现这一过程的理解涉及到超敏感性和双稳态的概念,这些概念与生化网络的非线性动力学相关,而忽略了空间因素。事实上,到目前为止,关于信号在细胞质中的传播所知甚少。在这项工作中,我们从非洲爪蟾卵母细胞中MAPK级联的米氏模型出发,构建了该级联的反应扩散模型。我们在一维空间中研究这个模型。基于先前关于反应扩散模型的一般结果,我们特别研究了我们模型中信号传播的条件。我们表明,传播前沿的存在敏感地依赖于质膜处的初始条件和边界条件。本文讨论了这一发现可能的生物学后果。

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