title: Glutamine analogs promote cytoophidium assembly in human and Drosophila cells.
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.
authors.affiliation: Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom.
authors.forename: Kangni
authors.initials: K
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Ömür Yilmaz
authors.initials: ÖY
authors.lastname: Tastan
authors.forename: Zillah Anne
authors.initials: ZA
authors.lastname: Deussen
authors.forename: Mayte Yu-Yin
authors.initials: MY
authors.lastname: Siswick
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001377:Azaserine / Q000031:analogs & derivatives / Q000494:pharmacology; D019731:Carbon-Nitrogen Ligases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002451:Cell Compartmentation / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D003980:Diazooxonorleucine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005973:Glutamine / Q000031:analogs & derivatives*; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009866:Oogenesis / Q000187:drug effects; D034622:RNA Interference
chemical_list: D004791:Enzyme Inhibitors; D003980:Diazooxonorleucine; D005973:Glutamine; D001377:Azaserine; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase