Cell shape and negative links in regulatory motifs together control spatial information flow in signaling networks

被引：215

作者：

Neves, Susana R. ^{[1
]}

Tsokas, Panayiotis ^{[1
]}

Sarkar, Anamika ^{[1
]}

Grace, Elizabeth A. ^{[1
]}

Rangamani, Padmini ^{[1
]}

Taubenfeld, Stephen M. ^{[2
]}

Alberini, Cristina M. ^{[2
]}

Schaff, James C. ^{[3
]}

Blitzer, Robert D. ^{[1
]}

Moraru, Ion I. ^{[3
]}

Iyengar, Ravi ^{[1
]}

机构：

[1] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA

[2] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA

[3] Univ Connecticut, Ctr Hlth, Ctr Cell Anal & Modeling, Farmington, CT 06030 USA

来源：

CELL | 2008年 / 133卷 / 04期

关键词：

D O I：

10.1016/j.cell.2008.04.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：666 / 680

页数：15

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