Pom1 gradient buffering through intermolecular auto‐phosphorylation

Molecular Systems Biology

Micha Hersch¹  Olivier Hachet²  Sascha Dalessi¹  Pranav Ullal²  Payal Bhatia²  Sven Bergmann¹ 

[1] Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland;Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland

关键词: auto‐catalysis;    cell cycle control;    fission yeast Schizosaccharomyces pombe;    gradient formation;    robustness;   

DOI  :  10.15252/msb.20145996

来源: Wiley

【 摘 要 】

Abstract

Concentration gradients provide spatial information for tissue patterning and cell organization, and their robustness under natural fluctuations is an evolutionary advantage. In rod-shaped Schizosaccharomyces pombe cells, the DYRK-family kinase Pom1 gradients control cell division timing and placement. Upon dephosphorylation by a Tea4-phosphatase complex, Pom1 associates with the plasma membrane at cell poles, where it diffuses and detaches upon auto-phosphorylation. Here, we demonstrate that Pom1 auto-phosphorylates intermolecularly, both in vitro and in vivo, which confers robustness to the gradient. Quantitative imaging reveals this robustness through two system's properties: The Pom1 gradient amplitude is inversely correlated with its decay length and is buffered against fluctuations in Tea4 levels. A theoretical model of Pom1 gradient formation through intermolecular auto-phosphorylation predicts both properties qualitatively and quantitatively. This provides a telling example where gradient robustness through super-linear decay, a principle hypothesized a decade ago, is achieved through autocatalysis. Concentration-dependent autocatalysis may be a widely used simple feedback to buffer biological activities.

Synopsis

Theoretical modeling and experimental data show that the DYRK-family kinase Pom1 auto-phosphorylates intermolecularly. This mechanism confers robustness to Pom1 concentration gradients through super-linear decay.

• The DYRK-family kinase Pom1 auto-phosphorylates intermolecularly in vivo and in vitro.
• Quantitative imaging of Pom1 gradient shows gradient robustness through two system's level properties.
• A theoretical model of Pom1 gradient formation through intermolecular auto-phosphorylation predicts these properties qualitatively and quantitatively.
• Thus, Pom1 gradients provide an example of gradient robustness through super-linear decay.

【 授权许可】

CC BY   
© 2015 The Authors. Published under the terms of the CC BY 4.0 license

Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.