title: Cytoophidium assembly reflects upregulation of IMPDH activity.
abstract: Cytidine triphosphate synthase (CTPS) and inosine monophosphate dehydrogenase (IMPDH) (both of which have two isoforms) can form fiber-like subcellular structures termed 'cytoophidia' under certain circumstances in mammalian cells. Although it has been shown that filamentation of CTPS downregulates its activity by disturbing conformational changes, the activity of IMPDH within cytoophidia is still unclear. Most previous IMPDH cytoophidium studies were performed under conditions involving inhibitors that impair GTP synthesis. Here, we show that IMPDH forms cytoophidia without inhibition of GTP synthesis. First, we find that an elevated intracellular CTP concentration or treatment with 3'-deazauridine, a CTPS inhibitor, promotes IMPDH cytoophidium formation and increases the intracellular GTP pool size. Moreover, restriction of cell growth triggers the disassembly of IMPDH cytoophidia, implying that their presence is correlated with active cell metabolism. Finally, we show that the presence of IMPDH cytoophidia in mouse pancreatic islet cells might correlate with nutrient uptake in the animal. Collectively, our findings reveal that formation of IMPDH cytoophidia reflects upregulation of purine nucleotide synthesis, suggesting that the IMPDH cytoophidium plays a role distinct from that of the CTPS cytoophidium in controlling intracellular nucleotide homeostasis.
authors: Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan, Republic of China.
authors: Chia-Chun
authors: CC
authors: Chang
authors: Molecular Medicine Research Center, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan, Republic of China.
authors: Wei-Cheng
authors: WC
authors: Lin
authors: Molecular Medicine Research Center, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan, Republic of China Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan, Republic of China Department of Biochemistry, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan, Republic of China.
authors: Li-Mei
authors: LM
authors: Pai
authors: Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan, Republic of China Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10051, Taiwan, Republic of China.
authors: Hsuan-Shu
authors: HS
authors: Lee
authors: Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan, Republic of China Department of Animal Science and Technology, National Taiwan University, Taipei 106, Taiwan, Republic of China.
authors: Shinn-Chih
authors: SC
authors: Wu
authors: Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan, Republic of China Department of Animal Science and Technology, National Taiwan University, Taipei 106, Taiwan, Republic of China.
authors: Shih-Torng
authors: ST
authors: Ding
authors: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK jilong.liu@dpag.ox.ac.uk liyingsung@ntu.edu.tw.
authors: Ji-Long
authors: JL
authors: Liu
authors: Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan, Republic of China Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, Republic of China jilong.liu@dpag.ox.ac.uk liyingsung@ntu.edu.tw.
authors: Li-Ying
authors: LY
authors: Sung
mesh_terms: D000818:Animals; D019731:Carbon-Nitrogen Ligases / Q000378:metabolism; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009711:Nucleotides / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D009711:Nucleotides; D007168:IMP Dehydrogenase; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase
keywords: CTPS; Cytoophidium; IMPDH; Nucleotide