Positional information generated by spatially distributed signaling cascades.

Authors

Javier Muñoz-García, School of Mathematical Sciences and Complex Adaptive Systems Laboratory, University College Dublin, Dublin, Ireland; Grupo Interdisciplinar de Sistemas Complejos (GISC), Madrid, SpainFollow
Zoltan Neufeld, School of Mathematical Sciences and Complex Adaptive Systems Laboratory, University College Dublin, Dublin, Ireland
Boris N Kholodenko, UCD Conway Institute, University College Dublin, Dublin, Ireland; Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PAFollow

Document Type

Article

Publication Date

3-1-2009

Comments

This article has been peer reviewed and is published in PLoS Computational Biology 2009, 5(3). The published version is available at DOI: 10.1371/journal.pcbi.1000330. © Public Library of Science

Abstract

The temporal and stationary behavior of protein modification cascades has been extensively studied, yet little is known about the spatial aspects of signal propagation. We have previously shown that the spatial separation of opposing enzymes, such as a kinase and a phosphatase, creates signaling activity gradients. Here we show under what conditions signals stall in the space or robustly propagate through spatially distributed signaling cascades. Robust signal propagation results in activity gradients with long plateaus, which abruptly decay at successive spatial locations. We derive an approximate analytical solution that relates the maximal amplitude and propagation length of each activation profile with the cascade level, protein diffusivity, and the ratio of the opposing enzyme activities. The control of the spatial signal propagation appears to be very different from the control of transient temporal responses for spatially homogenous cascades. For spatially distributed cascades where activating and deactivating enzymes operate far from saturation, the ratio of the opposing enzyme activities is shown to be a key parameter controlling signal propagation. The signaling gradients characteristic for robust signal propagation exemplify a pattern formation mechanism that generates precise spatial guidance for multiple cellular processes and conveys information about the cell size to the nucleus.

Recommended Citation

Muñoz-García, Javier; Neufeld, Zoltan; and Kholodenko, Boris N, "Positional information generated by spatially distributed signaling cascades." (2009). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 68.
https://jdc.jefferson.edu/pacbfp/68

PubMed ID

19300504