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A Design Principle for an Autonomous Post-translational Pattern Formation.

Shuhei S Sugai1, Koji L Ode2, Hiroki R Ueda2

  • 1Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.

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|April 27, 2017
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Summary
This summary is machine-generated.

A simple system with multisite phosphorylation can create complex spatial patterns, like stripes. This discovery simplifies pattern formation models by removing the need for complex molecular networks.

Keywords:
computational simulationpost-translational modificationreversible phosphorylationspatial patternstochastic simulationturing pattern

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Area of Science:

  • Biochemistry
  • Systems Biology
  • Theoretical Biology

Background:

  • Autonomous pattern formation often relies on intricate molecular and cellular networks.
  • Existing models frequently require pre-existing gradients or complex regulatory mechanisms.

Purpose of the Study:

  • To investigate if a simpler system can generate spatial patterns autonomously.
  • To identify the fundamental design principles for pattern formation using multisite phosphorylation.

Main Methods:

  • Theoretical modeling of a system with one substrate, multisite phosphorylation, and a kinase/phosphatase pair.
  • Utilizing a generic Michaelis-Menten scheme for (de-)phosphorylation reactions.
  • Extensive computational simulations (>23 million parameter sets) with freely diffusing species.

Main Results:

  • A system with multisite reversible post-translational modification can generate complex spatial patterns, including stripes.
  • Identified key design motifs: cyclic reactions and enzyme sequestration by slow-diffusing substrates.
  • These motifs create feedback loops (short-range positive, long-range negative) that induce Turing instability.
  • Pattern dimensions (width and height) are independently controllable via reaction-diffusion processes.

Conclusions:

  • Multisite reversible post-translational modification is a sufficient mechanism for autonomous pattern generation, negating the need for complex regulations like autocatalysis.
  • This mechanism is applicable to understanding subcellular protein localization driven by post-translational modifications.
  • Provides a simplified yet robust framework for understanding biological pattern formation.