The role of stochastic sequestration dynamics for intrinsic noise filtering in signaling network motifs

JOURNAL OF THEORETICAL BIOLOGY

卷:455

Article

Paul, Debdas¹  Radde, Nicole¹ 

[1] Univ Stuttgart, Inst Syst Theory & Automat Control, Pfaffenwaldring 9, D-70569 Stuttgart, Germany

关键词: Retroactivity;    Signaling cascade;    Stochastic modeling;    Dynamic sequestration;   

DOI  :  10.1016/j.jtbi.2018.07.012

来源: Elsevier

【 摘 要 】

The relation between design principles of signaling network motifs and their robustness against intrinsic noise still remains illusive. In this work we investigate the role of cascading for coping with intrinsic noise due to stochasticity in molecular reactions. We use stochastic approaches to quantify fluctuations in the terminal kinase of phosphorylation-dephosphorylation cascade motifs and demonstrate that cascading highly affects these fluctuations. We show that this purely stochastic effect can be explained by time-varying sequestration of upstream kinase molecules. In particular, we discuss conditions on time scales and parameter regimes which lead to a reduction of output fluctuations. Our results are put into biological context by adapting rate parameters of our modeling approach to biologically feasible ranges for general binding-unbinding and phosphorylation-dephosphorylation mechanisms. Overall, this study reveals a novel role of stochastic sequestration for dynamic noise filtering in signaling cascade motifs. (C) 2018 Elsevier Ltd. All rights reserved.

【 授权许可】

Free