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Limits to the rate of information transmission through the MAPK pathway.

ABSTRACT: Two important signalling pathways of NF-κB and ERK transmit merely 1 bit of information about the level of extracellular stimulation. It is thus unclear how such systems can coordinate complex cell responses to external cues. We analyse information transmission in the MAPK/ERK pathway that converts both constant and pulsatile EGF stimulation into pulses of ERK activity. Based on an experimentally verified computational model, we demonstrate that, when input consists of sequences of EGF pulses, transmitted information increases nearly linearly with time. Thus, pulse-interval transcoding allows more information to be relayed than the amplitude-amplitude transcoding considered previously for the ERK and NF-κB pathways. Moreover, the information channel capacity C, or simply bitrate, is not limited by the bandwidth B = 1/ τ, where τ ≈ 1 h is the relaxation time. Specifically, when the input is provided in the form of sequences of short binary EGF pulses separated by intervals that are multiples of τ/ n (but not shorter than τ), then for n = 2, C ≈ 1.39 bit h-1; and for n = 4, C ≈ 1.86 bit h-1. The capability to respond to random sequences of EGF pulses enables cells to propagate spontaneous ERK activity waves across tissue.

SUBMITTER: Grabowski F

PROVIDER: S-EPMC6451410 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Limits to the rate of information transmission through the MAPK pathway.

Grabowski Frederic F Czyż Paweł P Kochańczyk Marek M Lipniacki Tomasz T

Journal of the Royal Society, Interface 20190301 152

Two important signalling pathways of NF-κB and ERK transmit merely 1 bit of information about the level of extracellular stimulation. It is thus unclear how such systems can coordinate complex cell responses to external cues. We analyse information transmission in the MAPK/ERK pathway that converts both constant and pulsatile EGF stimulation into pulses of ERK activity. Based on an experimentally verified computational model, we demonstrate that, when input consists of sequences of EGF pulses, t ...[more]

PMID: 30836891

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Project description:All living things have evolved to sense changes in their environment in order to respond in adaptive ways. At the cellular level, these sensing systems generally involve receptor molecules at the cell surface, which detect changes outside the cell and relay those changes to the appropriate response elements downstream. With the advent of experimental technologies that can track signalling at the single-cell level, it has become clear that many signalling systems exhibit significant levels of 'noise,' manifesting as differential responses of otherwise identical cells to the same environment. This noise has a large impact on the capacity of cell signalling networks to transmit information from the environment. Application of information theory to experimental data has found that all systems studied to date encode less than 2.5 bits of information, with the majority transmitting significantly less than 1 bit. Given the growing interest in applying information theory to biological data, it is crucial to understand whether the low values observed to date represent some sort of intrinsic limit on information flow given the inherently stochastic nature of biochemical signalling events. In this work, we used a series of computational models to explore how much information a variety of common 'signalling motifs' can encode. We found that the majority of these motifs, which serve as the basic building blocks of cell signalling networks, can encode far more information (4-6 bits) than has ever been observed experimentally. In addition to providing a consistent framework for estimating information-theoretic quantities from experimental data, our findings suggest that the low levels of information flow observed so far in living system are not necessarily due to intrinsic limitations. Further experimental work will be needed to understand whether certain cell signalling systems actually can approach the intrinsic limits described here, and to understand the sources and purpose of the variation that reduces information flow in living cells.

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Limits to the rate of information transmission through the MAPK pathway.

Publications

Limits to the rate of information transmission through the MAPK pathway.

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