Interpreting frequency responses to dose-conserved pulsatile input signals in simple cell signaling motifs.
Many hormones are released in pulsatile patterns. This pattern can be modified, for instance by changing pulse frequency, to encode relevant physiological information. Often other properties of the pulse pattern will also change with frequency. How do signaling pathways of cells targeted by these ho...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3991699?pdf=render |
| _version_ | 1817983734265151488 |
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| author | Patrick A Fletcher Frédérique Clément Alexandre Vidal Joel Tabak Richard Bertram |
| author_facet | Patrick A Fletcher Frédérique Clément Alexandre Vidal Joel Tabak Richard Bertram |
| author_sort | Patrick A Fletcher |
| collection | DOAJ |
| description | Many hormones are released in pulsatile patterns. This pattern can be modified, for instance by changing pulse frequency, to encode relevant physiological information. Often other properties of the pulse pattern will also change with frequency. How do signaling pathways of cells targeted by these hormones respond to different input patterns? In this study, we examine how a given dose of hormone can induce different outputs from the target system, depending on how this dose is distributed in time. We use simple mathematical models of feedforward signaling motifs to understand how the properties of the target system give rise to preferences in input pulse pattern. We frame these problems in terms of frequency responses to pulsatile inputs, where the amplitude or duration of the pulses is varied along with frequency to conserve input dose. We find that the form of the nonlinearity in the steady state input-output function of the system predicts the optimal input pattern. It does so by selecting an optimal input signal amplitude. Our results predict the behavior of common signaling motifs such as receptor binding with dimerization, and protein phosphorylation. The findings have implications for experiments aimed at studying the frequency response to pulsatile inputs, as well as for understanding how pulsatile patterns drive biological responses via feedforward signaling pathways. |
| first_indexed | 2024-04-13T23:36:50Z |
| format | Article |
| id | doaj.art-228cbf757121475fbe86f43ef4ec413a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T23:36:50Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-228cbf757121475fbe86f43ef4ec413a2022-12-22T02:24:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9561310.1371/journal.pone.0095613Interpreting frequency responses to dose-conserved pulsatile input signals in simple cell signaling motifs.Patrick A FletcherFrédérique ClémentAlexandre VidalJoel TabakRichard BertramMany hormones are released in pulsatile patterns. This pattern can be modified, for instance by changing pulse frequency, to encode relevant physiological information. Often other properties of the pulse pattern will also change with frequency. How do signaling pathways of cells targeted by these hormones respond to different input patterns? In this study, we examine how a given dose of hormone can induce different outputs from the target system, depending on how this dose is distributed in time. We use simple mathematical models of feedforward signaling motifs to understand how the properties of the target system give rise to preferences in input pulse pattern. We frame these problems in terms of frequency responses to pulsatile inputs, where the amplitude or duration of the pulses is varied along with frequency to conserve input dose. We find that the form of the nonlinearity in the steady state input-output function of the system predicts the optimal input pattern. It does so by selecting an optimal input signal amplitude. Our results predict the behavior of common signaling motifs such as receptor binding with dimerization, and protein phosphorylation. The findings have implications for experiments aimed at studying the frequency response to pulsatile inputs, as well as for understanding how pulsatile patterns drive biological responses via feedforward signaling pathways.http://europepmc.org/articles/PMC3991699?pdf=render |
| spellingShingle | Patrick A Fletcher Frédérique Clément Alexandre Vidal Joel Tabak Richard Bertram Interpreting frequency responses to dose-conserved pulsatile input signals in simple cell signaling motifs. PLoS ONE |
| title | Interpreting frequency responses to dose-conserved pulsatile input signals in simple cell signaling motifs. |
| title_full | Interpreting frequency responses to dose-conserved pulsatile input signals in simple cell signaling motifs. |
| title_fullStr | Interpreting frequency responses to dose-conserved pulsatile input signals in simple cell signaling motifs. |
| title_full_unstemmed | Interpreting frequency responses to dose-conserved pulsatile input signals in simple cell signaling motifs. |
| title_short | Interpreting frequency responses to dose-conserved pulsatile input signals in simple cell signaling motifs. |
| title_sort | interpreting frequency responses to dose conserved pulsatile input signals in simple cell signaling motifs |
| url | http://europepmc.org/articles/PMC3991699?pdf=render |
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