Dataset Information

Core signalling motif displaying multistability through multi-state enzymes.

ABSTRACT: Bistability, and more generally multistability, is a key system dynamics feature enabling decision-making and memory in cells. Deciphering the molecular determinants of multistability is thus crucial for a better understanding of cellular pathways and their (re)engineering in synthetic biology. Here, we show that a key motif found predominantly in eukaryotic signalling systems, namely a futile signalling cycle, can display bistability when featuring a two-state kinase. We provide necessary and sufficient mathematical conditions on the kinetic parameters of this motif that guarantee the existence of multiple steady states. These conditions foster the intuition that bistability arises as a consequence of competition between the two states of the kinase. Extending from this result, we find that increasing the number of kinase states linearly translates into an increase in the number of steady states in the system. These findings reveal, to our knowledge, a new mechanism for the generation of bistability and multistability in cellular signalling systems. Further the futile cycle featuring a two-state kinase is among the smallest bistable signalling motifs. We show that multi-state kinases and the described competition-based motif are part of several natural signalling systems and thereby could enable them to implement complex information processing through multistability. These results indicate that multi-state kinases in signalling systems are readily exploited by natural evolution and could equally be used by synthetic approaches for the generation of multistable information processing systems at the cellular level.

SUBMITTER: Feng S

PROVIDER: S-EPMC5095215 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Core signalling motif displaying multistability through multi-state enzymes.

Feng Song S Sáez Meritxell M Wiuf Carsten C Feliu Elisenda E Soyer Orkun S OS

Journal of the Royal Society, Interface 20161001 123

Bistability, and more generally multistability, is a key system dynamics feature enabling decision-making and memory in cells. Deciphering the molecular determinants of multistability is thus crucial for a better understanding of cellular pathways and their (re)engineering in synthetic biology. Here, we show that a key motif found predominantly in eukaryotic signalling systems, namely a futile signalling cycle, can display bistability when featuring a two-state kinase. We provide necessary and s ...[more]

PMID: 27733693

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Project description:In multistability, a constant stimulus induces alternating perceptual interpretations. For many forms of visual multistability, the transition from one interpretation to another ("perceptual switch") is accompanied by a dilation of the pupil. Here we ask whether the same holds for auditory multistability, specifically auditory streaming. Two tones were played in alternation, yielding four distinct interpretations: the tones can be perceived as one integrated percept (single sound source), or as segregated with either tone or both tones in the foreground. We found that the pupil dilates significantly around the time a perceptual switch is reported ("multistable condition"). When participants instead responded to actual stimulus changes that closely mimicked the multistable perceptual experience ("replay condition"), the pupil dilated more around such responses than in multistability. This still held when data were corrected for the pupil response to the stimulus change as such. Hence, active responses to an exogeneous stimulus change trigger a stronger or temporally more confined pupil dilation than responses to an endogenous perceptual switch. In another condition, participants randomly pressed the buttons used for reporting multistability. In Study 1, this "random condition" failed to sufficiently mimic the temporal pattern of multistability. By adapting the instructions, in Study 2 we obtained a response pattern more similar to the multistable condition. In this case, the pupil dilated significantly around the random button presses. Albeit numerically smaller, this pupil response was not significantly different from the multistable condition. While there are several possible explanations-related, e.g., to the decision to respond-this underlines the difficulty to isolate a purely perceptual effect in multistability. Our data extend previous findings from visual to auditory multistability. They highlight methodological challenges in interpreting such data and suggest possible approaches to meet them, including a novel stimulus to simulate the experience of perceptual switches in auditory streaming.

Dataset Information

Core signalling motif displaying multistability through multi-state enzymes.

Publications

Core signalling motif displaying multistability through multi-state enzymes.

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