Nucleocytoplasmic shuttling of a GATA transcription factor functions as a development timer

Science. 2014 Mar 21;343(6177):1249531. doi: 10.1126/science.1249531.

Abstract

Biological oscillations are observed at many levels of cellular organization. In the social amoeba Dictyostelium discoideum, starvation-triggered multicellular development is organized by periodic cyclic adenosine 3',5'-monophosphate (cAMP) waves, which provide both chemoattractant gradients and developmental signals. We report that GtaC, a GATA transcription factor, exhibits rapid nucleocytoplasmic shuttling in response to cAMP waves. This behavior requires coordinated action of a nuclear localization signal and reversible G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor-mediated phosphorylation. Although both are required for developmental gene expression, receptor occupancy promotes nuclear exit of GtaC, which leads to a transient burst of transcription at each cAMP cycle. We demonstrate that this biological circuit filters out high-frequency signals and counts those admitted, thereby enabling cells to modulate gene expression according to the dynamic pattern of the external stimuli.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Cell Nucleus / metabolism*
  • Cyclic AMP / metabolism
  • Cyclic AMP / pharmacology
  • Cytoplasm / metabolism*
  • Dictyostelium / growth & development
  • Dictyostelium / metabolism*
  • GATA Transcription Factors / chemistry
  • GATA Transcription Factors / genetics
  • GATA Transcription Factors / metabolism*
  • Gene Expression Regulation
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Nuclear Localization Signals
  • Phosphorylation
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Receptors, G-Protein-Coupled / metabolism

Substances

  • GATA Transcription Factors
  • Nuclear Localization Signals
  • Protozoan Proteins
  • Receptors, G-Protein-Coupled
  • Cyclic AMP
  • Heterotrimeric GTP-Binding Proteins

Associated data

  • GEO/GSE54866