Glutamine analogs promote cytoophidium assembly in human and Drosophila cells

J Genet Genomics. 2011 Sep 20;38(9):391-402. doi: 10.1016/j.jgg.2011.08.004. Epub 2011 Aug 17.

Abstract

CTP synthase is compartmentalized within a subcellular structure, termed the cytoophidium, in a range of organisms including bacteria, yeast, fruit fly and rat. Here we show that CTP synthase is also compartmentalized into cytoophidia in human cells. Surprisingly, the occurrence of cytoophidia in human cells increases upon treatment with a glutamine analog 6-diazo-5-oxo-l-norleucine (DON), an inhibitor of glutamine-dependent enzymes including CTP synthase. Experiments in flies confirmed that DON globally promotes cytoophidium assembly. Clonal analysis via CTP synthase RNA interference in somatic cells indicates that CTP synthase expression level is critical for the formation of cytoophidia. Moreover, DON facilitates cytoophidium assembly even when CTP synthase level is low. A second glutamine analog azaserine also promotes cytoophidum formation. Our data demonstrate that glutamine analogs serve as useful tools in the study of cytoophidia.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Azaserine / analogs & derivatives
  • Azaserine / pharmacology
  • Carbon-Nitrogen Ligases / antagonists & inhibitors
  • Carbon-Nitrogen Ligases / deficiency
  • Carbon-Nitrogen Ligases / genetics
  • Carbon-Nitrogen Ligases / metabolism
  • Cell Compartmentation / drug effects*
  • Cell Cycle / drug effects
  • Diazooxonorleucine / analogs & derivatives
  • Diazooxonorleucine / pharmacology*
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / drug effects*
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / metabolism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Glutamine / analogs & derivatives*
  • HeLa Cells
  • Humans
  • Intracellular Space / drug effects*
  • Intracellular Space / enzymology
  • Intracellular Space / metabolism*
  • Male
  • Oogenesis / drug effects
  • RNA Interference

Substances

  • Enzyme Inhibitors
  • Diazooxonorleucine
  • Glutamine
  • Azaserine
  • Carbon-Nitrogen Ligases
  • CTP synthetase