A Design Principle for an Autonomous Post-translational Pattern Formation

Publication date: 25 April 2017
Source:Cell Reports, Volume 19, Issue 4
Author(s): Shuhei S. Sugai, Koji L. Ode, Hiroki R. Ueda
Previous autonomous pattern-formation models often assumed complex molecular and cellular networks. This theoretical study, however, shows that a system composed of one substrate with multisite phosphorylation and a pair of kinase and phosphatase can generate autonomous spatial information, including complex stripe patterns. All (de-)phosphorylation reactions are described with a generic Michaelis-Menten scheme, and all species freely diffuse without pre-existing gradients. Computational simulation upon >23,000,000 randomly generated parameter sets revealed the design motifs of cyclic reaction and enzyme sequestration by slow-diffusing substrates. These motifs constitute short-range positive and long-range negative feedback loops to induce Turing instability. The width and height of spatial patterns can be controlled independently by distinct reaction-diffusion processes. Therefore, multisite reversible post-translational modification can be a ubiquitous source for various patterns without requiring other complex regulations such as autocatalytic regulation of enzymes and is applicable to molecular mechanisms for inducing subcellular localization of proteins driven by post-translational modifications.

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Using computer simulations, Sugai et al. showed that a generic Michaelis-Menten scheme of two-site reversible phosphorylation can produce Turing patterns in the spatial distribution of a substrate's modification states. A random parameter search found typical combinations of reaction parameters accounting for the pattern formation and tuning the pattern shapes.


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