Interlinked GTPase cascades provide a motif for both robust switches and oscillators

Andreas Ehrmann; Basile Nguyen; Udo Seifert

doi:10.1098/rsif.2019.0198

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arXiv · 1903.11102

Interlinked GTPase cascades provide a motif for both robust switches and oscillators

Andreas Ehrmann·Basile Nguyen·Udo Seifert

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Abstract

GTPases regulate a wide range of cellular processes, such as intracellular vesicular transport, signal transduction, and protein translation. These hydrolase enzymes operate as biochemical switches by toggling between an active guanosine triphosphate (GTP)-bound state and an inactive guanosine diphosphate (GDP)-bound state. We compare two network motifs, a single-species switch and an interlinked cascade that consists of two species coupled through positive and negative feedback loops. We find that interlinked cascades are closer to the ideal all-or-none switch and are more robust against fluctuating signals. While the single-species switch can only achieve bistability, interlinked cascades can be converted into oscillators by tuning the cofactor concentrations, which catalyse the activity of the cascade. These regimes can only be achieved with sufficient chemical driving provided by GTP hydrolysis. In this study, we present a thermodynamically consistent model that can achieve bistability and oscillations with the same feedback motif.

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Andreas Ehrmann, Basile Nguyen, Udo Seifert. 2019-03-26. Interlinked GTPase cascades provide a motif for both robust switches and oscillators. https://doi.org/10.1098/rsif.2019.0198

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