Cell Growth Control by Stable Rbg2/Gir2 Complex Formation Under Amino Acid Starvation

Genes Cells. 2013 Oct;18(10):859-72. doi: 10.1111/gtc.12082. Epub 2013 Jul 31.

Abstract

The molecular fine-tuning mechanisms underlying adaptive responses to environmental stresses in eukaryotes remain largely unknown. Here, we report on a novel stress-induced cell growth control mechanism involving a highly conserved complex containing Rbg2 and Gir2 subunits, which are the budding yeast orthologs of human Drg2 and Dfrp2, respectively. We found that the complex is responsible for efficient cell growth under amino acid starvation. Using native PAGE analyses, we observed that, individually, Rbg2 and Gir2 were labile proteins. However, they formed a complex that stabilized each other, and this stability became significantly enhanced after amino acid starvation. We observed that the stabilization of the complex was strictly dependent on GDP or GTP binding to Rbg2. A point mutation (S77N) that inactivated nucleotide binding impaired formation of the complex and disrupted the stress-induced cell growth. Interestingly, the complex bound the translational activator Gcn1 in a dose-dependent manner according to the stress level, suggesting a dynamic association with the cellular translational machinery. We propose that the Rbg2/Gir2 complex is a modulator that maintains cellular homoeostasis, thus promoting the survival of eukaryotic organisms in stressful environments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / genetics
  • Amino Acids / metabolism*
  • Binding Sites
  • Cell Proliferation*
  • Evolution, Molecular
  • GTP Phosphohydrolases / chemistry
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • Gene Expression Regulation, Fungal
  • Homeostasis
  • Humans
  • Peptide Elongation Factors / chemistry
  • Peptide Elongation Factors / metabolism
  • Protein Binding
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Stress, Physiological*

Substances

  • Amino Acids
  • GCN1 protein, S cerevisiae
  • Gir2 protein, S cerevisiae
  • Peptide Elongation Factors
  • Saccharomyces cerevisiae Proteins
  • GTP Phosphohydrolases
  • Rbg2 protein, S cerevisiae