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

Gabriel N. Aughey, Stuart J. Grice, Qing Ji Shen, Yichi Xu, Chia Chun Chang, Ghows Azzam, Pei Yu Wang, Luke Freeman-Mills, Li Mei Pai, Li Ying Sung, Jun Yan, Ji Long Liu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

69 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1045-1056
Number of pages12
JournalBiology Open
Volume3
Issue number11
DOIs
StatePublished - 15 11 2014

Bibliographical note

Publisher Copyright:
©2014. Published by The Company of Biologists Ltd|.

Keywords

  • CTP
  • Ctp synthase
  • Cytoophidium
  • Drosophila
  • Intracellular compartmentation
  • Neurogenesis

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