Journal
EXPERIMENTAL CELL RESEARCH
Volume 405, Issue 2, Pages -Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2021.112684
Keywords
CTPS; Cytoophidium; Zebrafish
Categories
Funding
- ShanghaiTech University
- UK Medical Research Council [MC_UU_12021/3, MC_U137788471]
- National Natural Science Foundation of China [31771490]
- FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) [2017/20745-1]
- MRC [MC_U137788471, MC_UU_12021/3] Funding Source: UKRI
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CTPS catalyzes de novo CTP biosynthesis in zebrafish, forming cytoophidia that may regulate its activity and stability. Treatment with a CTPS inhibitor can induce more cytoophidia in certain tissues, shedding light on the physiological importance of this intracellular structure in vertebrates.
Cytidine triphosphate synthase (CTPS) catalyzes the rate-limiting step of de novo CTP biosynthesis. An intracellular structure of CTPS, the cytoophidium, has been found in many organisms including prokaryotes and eukaryotes. Formation of the cytoophidium has been suggested to regulate the activity and stability of CTPS and may participate in certain physiological events. Herein, we demonstrate that both CTPS1a and CTPS1b in zebrafish are able to form the cytoophidium in cultured cells. A point mutation, H355A, abrogates cytoophidium assembly of zebrafish CTPS1a and CTPS1b. In addition, we show the presence of CTPS cytoophidia in multiple tissues of larval and adult fish under normal conditions, while treatment with a CTPS inhibitor 6-diazo-5-oxo-L-norleucine (DON) can induce more cytoophidia in some tissues. Our findings reveal that forming the CTPS cytoophidium is a natural phenomenon of zebrafish and provide valuable information for future research on the physiological importance of this intracellular structure in vertebrates.
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