Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism.
Journal
Biology open
Journal Volume
3
Journal Issue
11
Start Page
1045
End Page
1056
ISSN
2046-6390
Date Issued
2014-10-17
Author(s)
Aughey, Gabriel N
Grice, Stuart J
Shen, Qing-Ji
Xu, Yichi
Azzam, Ghows
Freeman-Mills, Luke
Pai, Li-Mei
Yan, Jun
Liu, Ji-Long
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.
Subjects
CTP
CTP synthase
Drosophila
cytoophidium
intracellular compartmentation
neurogenesis
Publisher
Company of Biologists
Type
journal article