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Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity

A signaling pathway transmits information from an upstream system to downstream systems, ideally in a unidirectional fashion. A key obstacle to unidirectional transmission is retroactivity, the additional reaction flux that affects a system once its species interact with those of downstream systems....

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Detalles Bibliográficos
Autores principales: Shah, Rushina, Del Vecchio, Domitilla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Biophysical Society 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549655/
https://www.ncbi.nlm.nih.gov/pubmed/28793226
http://dx.doi.org/10.1016/j.bpj.2017.06.019
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author Shah, Rushina
Del Vecchio, Domitilla
author_facet Shah, Rushina
Del Vecchio, Domitilla
author_sort Shah, Rushina
collection PubMed
description A signaling pathway transmits information from an upstream system to downstream systems, ideally in a unidirectional fashion. A key obstacle to unidirectional transmission is retroactivity, the additional reaction flux that affects a system once its species interact with those of downstream systems. This raises the fundamental question of whether signaling pathways have developed specialized architectures that overcome retroactivity and transmit unidirectional signals. Here, we propose a general procedure based on mathematical analysis that provides an answer to this question. Using this procedure, we analyze the ability of a variety of signaling architectures to transmit one-way (from upstream to downstream) signals, as key biological parameters are tuned. We find that single stage phosphorylation and phosphotransfer systems that transmit signals from a kinase show a stringent design tradeoff that hampers their ability to overcome retroactivity. Interestingly, cascades of these architectures, which are highly represented in nature, can overcome this tradeoff and thus enable unidirectional transmission. By contrast, phosphotransfer systems, and single and double phosphorylation cycles that transmit signals from a substrate, are unable to mitigate retroactivity effects, even when cascaded, and hence are not well suited for unidirectional information transmission. These results are largely independent of the specific reaction-rate constant values, and depend on the topology of the architectures. Our results therefore identify signaling architectures that, allowing unidirectional transmission of signals, embody modular processes that conserve their input/output behavior across multiple contexts. These findings can be used to decompose natural signal transduction networks into modules, and at the same time, they establish a library of devices that can be used in synthetic biology to facilitate modular circuit design.
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spelling pubmed-55496552018-08-08 Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity Shah, Rushina Del Vecchio, Domitilla Biophys J Systems Biophysics A signaling pathway transmits information from an upstream system to downstream systems, ideally in a unidirectional fashion. A key obstacle to unidirectional transmission is retroactivity, the additional reaction flux that affects a system once its species interact with those of downstream systems. This raises the fundamental question of whether signaling pathways have developed specialized architectures that overcome retroactivity and transmit unidirectional signals. Here, we propose a general procedure based on mathematical analysis that provides an answer to this question. Using this procedure, we analyze the ability of a variety of signaling architectures to transmit one-way (from upstream to downstream) signals, as key biological parameters are tuned. We find that single stage phosphorylation and phosphotransfer systems that transmit signals from a kinase show a stringent design tradeoff that hampers their ability to overcome retroactivity. Interestingly, cascades of these architectures, which are highly represented in nature, can overcome this tradeoff and thus enable unidirectional transmission. By contrast, phosphotransfer systems, and single and double phosphorylation cycles that transmit signals from a substrate, are unable to mitigate retroactivity effects, even when cascaded, and hence are not well suited for unidirectional information transmission. These results are largely independent of the specific reaction-rate constant values, and depend on the topology of the architectures. Our results therefore identify signaling architectures that, allowing unidirectional transmission of signals, embody modular processes that conserve their input/output behavior across multiple contexts. These findings can be used to decompose natural signal transduction networks into modules, and at the same time, they establish a library of devices that can be used in synthetic biology to facilitate modular circuit design. The Biophysical Society 2017-08-08 2017-08-08 /pmc/articles/PMC5549655/ /pubmed/28793226 http://dx.doi.org/10.1016/j.bpj.2017.06.019 Text en © 2017 Biophysical Society. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Systems Biophysics
Shah, Rushina
Del Vecchio, Domitilla
Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity
title Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity
title_full Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity
title_fullStr Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity
title_full_unstemmed Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity
title_short Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity
title_sort signaling architectures that transmit unidirectional information despite retroactivity
topic Systems Biophysics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549655/
https://www.ncbi.nlm.nih.gov/pubmed/28793226
http://dx.doi.org/10.1016/j.bpj.2017.06.019
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