Cytoophidia coupling adipose architecture and metabolism

Liu, Jingnan; Zhang, Yuanbing; Zhou, Youfang; Wang, Qiao-Qi; Ding, Kang; Zhao, Suwen; Lü, Peng; Liu, Ji‐Long

doi:10.1007/s00018-022-04567-w

Cited by 18 publications

(32 citation statements)

References 60 publications

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“…In order to find out whether the abnormality is caused by the inability of CTPS to aggregate due to H355A point mutation or the addition of mCherry tag, our laboratory constructed another Drosophila strain with mCherry added to the C-terminus of CTPS based on w 1118 . To determine whether the feature of cytoophidium localization was in fact introduced by protein fusion between CTPS and mCherry tag, we performed immunofluorescence microscopy and directly detected the CTPS protein of the w 1118 fly and found no difference [ 27 ]. It is proven by the observation that the knock-in mCherry tag does not affect the polymerization of CTPS protein.…”

Section: Resultsmentioning

confidence: 99%

“…However, we could not simply rescue the phenotypes found in the CTPS H355A -mCh mutant by expressing CTPS-mCherry protein. Our previous studies in mammals [ 26 ] and Drosophila [ 27 ] confirmed that the CTPS H355A point mutation is dominant-negative, which is to say that as long as the CTPS H355A protein exists, the CTPS protein would not be able to assemble into cytoophidium [ 26 , 27 ]. Because the H355A point mutation of CTPS would disrupt the assembly of the cytoophidia dominant negatively, we have analyzed the CTPS H355A/TM6B -mCh egg chambers and found that CTPS H355A/TM6B also have defects in follicle epithelial integrity mentioned above ( Supplementary Figure S1 ).…”

Section: Discussionmentioning

confidence: 99%

“…Both w 1118 and C-terminal mChe-4V5 tagged CTPS knock-in flies out of w 1118 produced in our laboratory were used as wild-type controls unless stated otherwise. The stocks used were: (1) CTPS H335A mutated with mChe-4V5 tagged CTPS Knock-in fly , (2) Actin-Gal4/Cyo (A gift from Guanjun Gao’s lab, ubiquitous expression under strong promoter, a chromosome II insertion balanced over Curly of Oster [ 32 ]), (3) Tj-Gal4 (A gift from Kun Dou’s lab [ 33 , 34 ]), (4) Sp/Cyo; Sb/Tm6B (Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Drosophila Resources and Technology Platform), (5) UAS CTPS-mCherry-OE, and UAS CTPS H355A -mCherry-OE [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

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Cytoophidia Maintain the Integrity of Drosophila Follicle Epithelium

Wang

You

Liu

2022

IJMS

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CTP synthase (CTPS) forms a filamentous structure termed the cytoophidium in all three domains of life. The female reproductive system of Drosophila is an excellent model for studying the physiological function of cytoophidia. Here, we use CTPSH355A, a point mutation that destroys the cytoophidium-forming ability of CTPS, to explore the in vivo function of cytoophidia. In CTPSH355A egg chambers, we observe the ingression and increased heterogeneity of follicle cells. In addition, we find that the cytoophidium-forming ability of CTPS, rather than the protein level, is the cause of the defects observed in CTPSH355A mutants. To sum up, our data indicate that cytoophidia play an important role in maintaining the integrity of follicle epithelium.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Cytoophidia Maintain the Integrity of Drosophila Follicle Epithelium

Wang

You

Liu

2022

IJMS

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“…Describing their shape vividly, the word “cytoophidia” means “cellular snakes” in Greek. Cytoophidia were found in many species in all three domains of life, which means cytoophidia are conserved in evolution [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Super-Resolution Imaging Reveals Dynamic Reticular Cytoophidia

Fang

et al. 2022

IJMS

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CTP synthase (CTPS) can form filamentous structures termed cytoophidia in cells in all three domains of life. In order to study the mesoscale structure of cytoophidia, we perform fluorescence recovery after photobleaching (FRAP) and stimulated emission depletion (STED) microscopy in human cells. By using an EGFP dimeric tag as a tool to explore the physical properties of cytoophidia, we find that cytoophidia are dynamic and reticular. The reticular structure of CTPS cytoophidia may provide space for other components, such as IMPDH. In addition, we observe CTPS granules with tentacles.

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“…Drosophila have served as a classic model for studying CTPS cytoophidia [25]. Through experiments involving point mutations and others, CTPS cytoophidia have been found to have close ties to adipose tissue architecture [26].…”

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Filamentation and inhibition of prokaryotic CTP synthase

Guo,

Wang,

Liu

2023

Preprint

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CTP synthase (CTPS) plays a pivotal role in the de novo synthesis of CTP, a fundamental building block for RNA and DNA, which is essential for life. CTPS is capable of directly binding to all four nucleotide triphosphates: ATP, UTP, CTP, and GTP. Furthermore, CTPS can form cytoophidia in vivo and metabolic filaments in vitro, undergoing regulation at multiple levels. CTPS is considered a potential therapeutic target for combating invasions or infections by virus or prokaryotic pathogens. Utilizing cryo-electron microscopy, we have determined the structure ofEscherichia coliCTPS (ecCTPS) filament in complex with CTP, NADH, and the covalent inhibitor DON, achieving a resolution of 2.8Å. We construct a phylogenetic tree based on differences in filament-forming interfaces and design a variant to validate our hypothesis, providing an evolutionary perspective on the CTPS filament formation. Our computational analysis reveals a solvent-accessible ammonia tunnel upon DON binding. By comparative structural analysis, we discern a distinct mode of CTP binding of ecCTPS, differing from eukaryotic counterparts. Combining biochemical assays and structural analysis, we determine and validate the synergistic inhibitory effects of CTP with NADH or adenine on CTPS. Our results expand our comprehension of diverse regulatory aspects of CTPS and lay a foundation for the design of specific inhibitors targeting prokaryotic CTPS.

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Cytoophidia coupling adipose architecture and metabolism

Cited by 18 publications

References 60 publications

Cytoophidia Maintain the Integrity of Drosophila Follicle Epithelium

Cytoophidia Maintain the Integrity of Drosophila Follicle Epithelium

Super-Resolution Imaging Reveals Dynamic Reticular Cytoophidia

Filamentation and inhibition of prokaryotic CTP synthase

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