Neves2008 - Role of cell shape and size in controlling intracellular signalling

Neves2008 - Role of cell shape and size in controlling intracellular signalling
The role of cell shape and size in the flow of spatial information from the cell surface receptor to downstream components within the cell has been studied on the β-adrenergic receptor to MAPK-signalling network.

This model is described in the article:
Cell shape and negative links in regulatory motifs together control spatial information flow in signaling networks.

Neves SR, Tsokas P, Sarkar A, Grace EA, Rangamani P, Taubenfeld SM, Alberini CM, Schaff JC, Blitzer RD, Moraru II, Iyengar R
Cell. 2008, 133(4):666-680
Abstract:
The role of cell size and shape in controlling local intracellular signaling reactions, and how this spatial information originates and is propagated, is not well understood. We have used partial differential equations to model the flow of spatial information from the beta-adrenergic receptor to MAPK1,2 through the cAMP/PKA/B-Raf/MAPK1,2 network in neurons using real geometries. The numerical simulations indicated that cell shape controls the dynamics of local biochemical activity of signal-modulated negative regulators, such as phosphodiesterases and protein phosphatases within regulatory loops to determine the size of microdomains of activated signaling components. The model prediction that negative regulators control the flow of spatial information to downstream components was verified experimentally in rat hippocampal slices. These results suggest a mechanism by which cellular geometry, the presence of regulatory loops with negative regulators, and key reaction rates all together control spatial information transfer and microdomain characteristics within cells.

This model is hosted on BioModels Database
and identified
by: MODEL8609366518
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.

To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.

Neves2008 — 细胞形状与大小在细胞内信号调控中的作用

细胞形状与大小在介导细胞表面受体至胞内下游组分的空间信息流动中的作用，已通过β-肾上腺素能受体（β-adrenergic receptor）到丝裂原活化蛋白激酶（MAPK）信号网络的研究得到阐释。

本模型对应的发表文章为：
《细胞形状与调控基序中的负相互连接共同控制信号网络中的空间信息流动》

作者：Neves SR、Tsokas P、Sarkar A、Grace EA、Rangamani P、Taubenfeld SM、Alberini CM、Schaff JC、Blitzer RD、Moraru II、Iyengar R

发表期刊：《细胞》（Cell）. 2008, 133(4):666-680

摘要：
细胞大小与形状在调控局部胞内信号反应中的作用，以及这类空间信息的起源与传播机制，目前尚未得到充分阐明。本研究借助偏微分方程，利用神经元的真实几何形态，构建了从β-肾上腺素能受体经环磷酸腺苷（cAMP）/蛋白激酶A（PKA）/B-Raf通路至丝裂原活化蛋白激酶1,2（MAPK1,2）的空间信息流动模型。数值模拟结果显示，细胞形状可调控信号调控环路中受信号修饰的负调控因子（如磷酸二酯酶与蛋白磷酸酶）的局部生化活性动态，进而决定激活信号组分的微域尺寸。本模型提出的“负调控因子可调控空间信息向下游组分的流动”这一预测，已在大鼠海马脑片实验中得到验证。上述结果揭示了一种由细胞几何形态、含负调控因子的调控环路以及关键反应速率共同调控胞内空间信息传递与微域特性的机制。

本模型存储于BioModels数据库（BioModels Database），编号为：MODEL8609366518。

如需引用BioModels数据库，请使用以下著录格式：《BioModels数据库：面向已发表定量动力学模型的增强型人工整理与注释资源》。

在法律允许的最大范围内，本编码模型的全部著作权及相关或邻接权利已在全球范围内捐赠至公共领域。如需了解更多信息，请参阅CC0公共领域贡献声明（CC0 Public Domain Dedication）。