Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism

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  • Gabriel N. Aughey
    Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom
  • Stuart J. Grice
    Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom
  • Qing-Ji Shen
    Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom
  • Yichi Xu
    CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
  • Chia-Chun Chang
    Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan, Republic of China
  • Ghows Azzam
    Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom
  • Pei-Yu Wang
    Department of Biochemistry, College of Medicine, Chang Gung University, Tao-Yuan, 333, Taiwan, Republic of China
  • Luke Freeman-Mills
    Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom
  • Li-Mei Pai
    Department of Biochemistry, College of Medicine, Chang Gung University, Tao-Yuan, 333, Taiwan, Republic of China
  • Li-Ying Sung
    Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan, Republic of China
  • Jun Yan
    CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
  • Ji-Long Liu
    Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom

Description

<jats:title>ABSTRACT</jats:title> <jats:p>The essential metabolic enzyme CTP synthase (CTPsyn) can be compartmentalised to form an evolutionarily-conserved intracellular structure termed the cytoophidium. Recently, it has been demonstrated that the enzymatic activity of CTPsyn is attenuated by incorporation into cytoophidia in bacteria and yeast cells. Here we demonstrate that CTPsyn is regulated in a similar manner in Drosophila tissues in vivo. We show that cytoophidium formation occurs during nutrient deprivation in cultured cells, as well as in quiescent and starved neuroblasts of the Drosophila larval central nervous system. We also show that cytoophidia formation is reversible during neurogenesis, indicating that filament formation regulates pyrimidine synthesis in a normal developmental context. Furthermore, our global metabolic profiling demonstrates that CTPsyn overexpression does not significantly alter CTPsyn-related enzymatic activity, suggesting that cytoophidium formation facilitates metabolic stabilisation. In addition, we show that overexpression of CTPsyn only results in moderate increase of CTP pool in human stable cell lines. Together, our study provides experimental evidence, and a mathematical model, for the hypothesis that inactive CTPsyn is incorporated into cytoophidia.</jats:p>

Journal

  • Biology Open

    Biology Open 3 (11), 1045-1056, 2014-10-17

    The Company of Biologists

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