3.8 Article

Information-theoretic analyses of cellular strategies for achieving high signaling capacity-dynamics, cross-wiring, and heterogeneity of cellular states

Journal

CURRENT OPINION IN SYSTEMS BIOLOGY
Volume 27, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.coisb.2021.06.003

Keywords

Signaling pathways; Hormones; Growth factors; or cytokines; Signaling dynamics; Cross-wired signaling; Shannon information; Fisher information

Funding

  1. Foundation for Polish Science [First TEAM/2017-3/21]
  2. European Union under the European Regional Development Fund
  3. Polish National Science Centre [PRELUDIUM 2019/33/N/NZ2/02691]

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Eukaryotic cells sense ligands through receptors and pathways, activating different effectors and leading to cross-wired signaling. The variability of signaling effectors in cells poses challenges in interpreting cellular signaling and heterogeneous responses.
An individual eukaryotic cell senses identity and quantity of ligands through molecular receptors and signaling pathways, dynamically activating signaling effectors. A distinct ligand often activates multiple different effectors, and a distinct effector is activated by numerous different ligands, which results in cross-wired signaling. In apparently identical cells, the activity of signaling effectors can vary considerably, raising questions about the accuracy of cellular signaling and the interpretation of heterogeneous responses, as either functional or simply noise. Cell-to-cell variability of signaling outcomes, signaling dynamics, and cross-wiring all give rise to signaling complexity, complicating the analysis of signaling mechanisms. Here, we consider a simple input-output modeling approach of information theory that is suitable to analyze signaling complexity and highlight recent studies that have advanced our understanding of the role different components of signaling complexity play in achieving effective information transfer along cellular signaling pathways.

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