4.6 Article

Gm14230 controls Tbc1d24 cytoophidia and neuronal cellular juvenescence

期刊

PLOS ONE
卷 16, 期 4, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0248517

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资金

  1. Morinaga Service Society
  2. Kato Memorial Bioscience Foundation
  3. Japan Epilepsy Research Foundation (JERF)
  4. Hoansha Foundation
  5. MSD Life Science Foundation
  6. Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care
  7. Japan Brain Foundation
  8. Takeda Science Foundation
  9. Japan Spina Bifida & Hydrocephalus Research Foundation
  10. Japan Intractable Diseases (Nanbyo) Research Foundation
  11. JSPS KAKENHI Grant [15H01486, 18K07788, 19H04774]
  12. Leading Initiative for Excellent Young Researchers (LEADER) [5013323]
  13. Initiative on Rare and Undiagnosed Diseases (IRUD) of AMED
  14. Grants-in-Aid for Scientific Research [15H01486, 18K07788, 19H04774] Funding Source: KAKEN

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Research has shown that the protein Tbc1d24 forms unique cellular structures called cytoophidia in neuronal cells, which are different from other types of cytoophidia. The formation of Tbc1d24 cytoophidia is influenced by cellular juvenescence and affects its enzymatic activity.
It is not fully understood how enzymes are regulated in the tiny reaction field of a cell. Several enzymatic proteins form cytoophidia, a cellular macrostructure to titrate enzymatic activities. Here, we show that the epileptic encephalopathy-associated protein Tbc1d24 forms cytoophidia in neuronal cells both in vitro and in vivo. The Tbc1d24 cytoophidia are distinct from previously reported cytoophidia consisting of inosine monophosphate dehydrogenase (Impdh) or cytidine-5'-triphosphate synthase (Ctps). Tbc1d24 cytoophidia is induced by loss of cellular juvenescence caused by depletion of Gm14230, a juvenility-associated lncRNA (JALNC) and zeocin treatment. Cytoophidia formation is associated with impaired enzymatic activity of Tbc1d24. Thus, our findings reveal the property of Tbc1d24 to form cytoophidia to maintain neuronal cellular juvenescence.

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