Abstract
The dynamic signal encoding paradigm suggests that information flows from the extracellular environment into specific signaling patterns (encoding) that are then read by downstream effectors to control cellular behavior. Previous work empirically quantified the information content of dynamic signaling patterns. However, whether this information can be faithfully transmitted to the gene expression level is unclear. Here we used NFkB signaling as a model to understand the accuracy of information transmission from signaling dynamics into gene expression. Using a detailed mathematical model, we simulated realistic NFkB signaling patterns with different degrees of variability. The NFkB patterns were used as an input to a simple gene expression model. Analysis of information transmission between ligand and NFkB and ligand and gene expression allows us to determine information loss in transmission between receptors to dynamic signaling patterns and between signaling dynamics to gene expression. Information loss could occur due to biochemical noise or due to a lack of specificity. We found that noise-free gene expression has very little information loss suggesting that gene expression can preserve specificity in NFkB patterns. As expected, the addition of noise to the gene expression model results in information loss. Interestingly, this effect can be mitigated by a specific choice of parameters that can substantially reduce information loss due to biochemical noise during gene expression. Overall our results show that the cellular capacity for information transmission from dynamic signaling patterns to gene expression can be high enough to preserve ligand specificity and thereby the accuracy of cellular response to environmental cues.
Highlights
IntroductionA ligand binding to a receptor initiates a cascade of biochemical transformations of cellular kinases, phosphatase, and other enzymes that connect the receptor to downstream effectors, often to change gene expression patterns [1]
The ability of cells to respond to environmental changes is key to their function
We present an analysis of the accuracy of information transmission from signaling dynamics into gene expression in the case of the transcription factor NFkB
Summary
A ligand binding to a receptor initiates a cascade of biochemical transformations of cellular kinases, phosphatase, and other enzymes that connect the receptor to downstream effectors, often to change gene expression patterns [1]. These cascades of events were divided into distinct pathways. The pathway paradigm was appealing because it was easy to understand how information about ligand identity and abundance is preserved. The complexity of signaling networks with a large degree of crosstalk and feedback shifted the paradigm from pathway to network-centric view [2]. If the mapping between ligands and signaling nodes is many to many, how does specificity, i.e. information about ligand identify and concentration, is preserved?
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