mTOR-S6K1 pathway mediates cytoophidium assembly

J Genet Genomics. 2019 Feb;46(2):65-74. doi: 10.1016/j.jgg.2018.11.006. Epub 2019 Jan 31.

Abstract

CTP synthase (CTPS), the rate-limiting enzyme in de novo CTP biosynthesis, has been demonstrated to assemble into evolutionarily conserved filamentous structures, termed cytoophidia, in Drosophila, bacteria, yeast and mammalian cells. However, the regulation and function of the cytoophidium remain elusive. Here, we provide evidence that the mechanistic target of rapamycin (mTOR) pathway controls cytoophidium assembly in mammalian and Drosophila cells. In mammalian cells, we find that inhibition of mTOR pathway attenuates cytoophidium formation. Moreover, CTPS cytoophidium assembly appears to be dependent on the mTOR complex 1 (mTORC1) mainly. In addition, knockdown of the mTORC1 downstream target S6K1 can inhibit cytoophidium formation, while overexpression of the constitutively active S6K1 reverses mTOR knockdown-induced cytoophidium disassembly. Finally, reducing mTOR protein expression results in a decrease of the length of cytoophidium in Drosophila follicle cells. Therefore, our study connects CTPS cytoophidium formation with the mTOR signaling pathway.

Keywords: CTP synthase; Colorectal cancer cell; Cytoophidium; Drosophila; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon-Nitrogen Ligases / chemistry
  • Carbon-Nitrogen Ligases / metabolism*
  • Cell Line, Tumor
  • Cytoplasm / metabolism
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / metabolism
  • Humans
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • ribosomal protein S6 kinase, 70kD, polypeptide 1
  • Carbon-Nitrogen Ligases
  • CTP synthetase