Distributed and dynamic intracellular organization of extracellular information

Proc Natl Acad Sci U S A. 2018 Jun 5;115(23):6088-6093. doi: 10.1073/pnas.1716659115. Epub 2018 May 21.

Abstract

Although cells respond specifically to environments, how environmental identity is encoded intracellularly is not understood. Here, we study this organization of information in budding yeast by estimating the mutual information between environmental transitions and the dynamics of nuclear translocation for 10 transcription factors. Our method of estimation is general, scalable, and based on decoding from single cells. The dynamics of the transcription factors are necessary to encode the highest amounts of extracellular information, and we show that information is transduced through two channels: Generalists (Msn2/4, Tod6 and Dot6, Maf1, and Sfp1) can encode the nature of multiple stresses, but only if stress is high; specialists (Hog1, Yap1, and Mig1/2) encode one particular stress, but do so more quickly and for a wider range of magnitudes. In particular, Dot6 encodes almost as much information as Msn2, the master regulator of the environmental stress response. Each transcription factor reports differently, and it is only their collective behavior that distinguishes between multiple environmental states. Changes in the dynamics of the localization of transcription factors thus constitute a precise, distributed internal representation of extracellular change. We predict that such multidimensional representations are common in cellular decision-making.

Keywords: cell signaling; mutual information; stress; time series; transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cytoplasm / metabolism
  • DNA-Binding Proteins / metabolism
  • Environment
  • Extracellular Space / physiology
  • Gene Expression Regulation, Fungal / genetics
  • Gene-Environment Interaction*
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Biological
  • Protein Transport
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomycetales / metabolism
  • Signal Transduction
  • Stress, Physiological
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology

Substances

  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Cyclic AMP-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases