CTPS and IMPDH form cytoophidia in developmental thymocytes

Peng, Min; Chang, Chi Ching; Liu, Ji‐Long; Sung, Li-Ying

doi:10.1016/j.yexcr.2021.112662

Cited by 23 publications

(15 citation statements)

References 46 publications

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“…Forming the cytoophidium can also attenuate CTPS ubiquitination and protect CTPS from proteasomal degradation (Lin et al, 2018;Sun and Liu, 2019a). Assembly of both CTPS and IMPDH cytoophidium has been shown positively correlated with mTORC activity, active glycolysis and rapid cell proliferation in cell types including lymphocytes and certain cancers, suggesting their physiological importance (Calise et al, 2018;Chang et al, 2015;Duong-Ly et al, 2018;Keppeke et al, 2019;Keppeke et al, 2018;Peng et al, 2021;Sun and Liu, 2019b).…”

Section: Introductionmentioning

confidence: 99%

Molecular crowding facilitates bundling of IMPDH polymers and cytoophidium formation

Chang

Peng

Zhong

et al. 2022

Cell. Mol. Life Sci.

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The cytoophidium is a unique type of membraneless compartment comprising of filamentous protein polymers. Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step of de novo GTP biosynthesis and plays critical roles in active cell metabolism. However, the molecular regulation of cytoophidium formation is poorly understood. Here we show that human IMPDH2 polymers bundle up to form cytoophidium-like aggregates in vitro when macromolecular crowders are present. The self-association of IMPDH polymers is suggested to rely on electrostatic interactions. In cells, the increase of molecular crowding with hyperosmotic medium induces cytoophidia, while the decrease of that by the inhibition of RNA synthesis perturbs cytoophidium assembly. In addition to IMPDH, CTPS and PRPS cytoophidium could be also induced by hyperosmolality, suggesting a universal phenomenon of cytoophidium-forming proteins. Finally, our results indicate that the cytoophidium can prolong the half-life of IMPDH, which is proposed to be one of conserved functions of this subcellular compartment.

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Section: Introductionmentioning

confidence: 99%

Molecular crowding facilitates bundling of IMPDH polymers and cytoophidium formation

Chang

Peng

Zhong

et al. 2022

Cell. Mol. Life Sci.

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“…Notably, CTPS has been observed to form filamentous structures termed cytoophidia in a wide range of organisms from prokaryotes to eukaryotes. Cytoophidia have been identified in Drosophila , Caulobacter crescentus , and S. cerevisiae since 2010 [2–4], with subsequent studies confirming their presence in human cells [5][6], fission yeast [7], plants [8], archaea [9], and mammalian cells [10]. These findings highlight the highly conserved nature of cytoophidia among different organisms and suggest that they possess significant yet undiscovered biological functions.…”

Section: Introductionmentioning

confidence: 94%

Cytoophidia influence cell cycle and size inSchizosaccharomyces pombe

Deng,

Li,

Liu

2023

Preprint

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CTP synthase (CTPS) forms cytoophidia in all three domains of life. Here we focus on the function of cytoophidia in cell proliferation using Schizosaccharomyces pombe as a model system. We find that converting His359 of CTPS into Ala359 leads to cytoophidium disassembly. By reducing the level of CTPS protein or specific point mutations, the loss of cytoophidia prolongs the G2 phase and expands cell size. In addition, the loss-filament mutant of CTPS leads to a decrease in the expression of genes related to G2/M transition and cell growth, including slm9. The overexpression of slm9 alleviates the G2 phase elongation and cell size enlargement induced by CTPS loss-filament mutant. Overall, our results connect cytoophidia with cell cycle and cell size control in Schizosaccharomyces pombe.

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“…For instance, CTPS cytoophidia are widely displayed by Drosophila tissues, especially in proliferative cell types [37][38][39] . In mammalian models, CTPS cytoophidia were found in mouse thymus and multiple human cancers 40,41 . The cytoophidium may also serve to protect its component proteins from degradation 42,43 .…”

Section: The Determinant Of Forming Either Open or Closed Hexamers Ismentioning

confidence: 99%

Allosteric inhibition of PRPS is moderated by filamentous polymerization

Chang

et al. 2022

Preprint

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Phosphoribosyl pyrophosphate (PRPP) is an important intermediate for the biosynthesis of purine and pyrimidine nucleotides, histidine, tryptophan, and cofactors NAD and NADP. Abnormal regulation of PRPP synthase (PRPS) has been associated with human disorders including Arts syndrome, retinal dystrophy and gouty arthritis. Recent studies have revealed that PRPS can form filamentous cytoophidia in prokaryotes and eukaryotes. Here we resolve two distinct filament structures of E. coli PRPS at near-atomic resolution under Cryo-EM. Formation of two types of filaments is controlled by the binding of different ligands. While the type A filament attenuates the allosteric inhibition of PRPS by ADP, the type B filament enhances the inhibition. In addition, a novel conformation of the regulatory flexible loop of PRPS was found occupying the ATP binding site. AMP/ADP bound at a noncanonical allosteric site interacts with the regulatory flexible loop and facilitates the binding of ATP. Our findings not only reveal molecular mechanisms of the regulation of PRPS with structural basis, but also suggest a distinctive bidirectional regulatory system for PRPP production via PRPS polymerization.

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CTPS and IMPDH form cytoophidia in developmental thymocytes

Cited by 23 publications

References 46 publications

Molecular crowding facilitates bundling of IMPDH polymers and cytoophidium formation

Molecular crowding facilitates bundling of IMPDH polymers and cytoophidium formation

Cytoophidia influence cell cycle and size inSchizosaccharomyces pombe

Allosteric inhibition of PRPS is moderated by filamentous polymerization

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