Gm14230 controls Tbc1d24 cytoophidia and neuronal cellular juvenescence

Takao Morimune; Ayami Tano; Yuya Tanaka; Haruka Yukiue; Takefumi Yamamoto; Ikuo Tooyama; Yoshihiro Maruo; Masaki Nishimura; Masaki Mori

doi:10.1371/journal.pone.0248517

Gm14230 controls Tbc1d24 cytoophidia and neuronal cellular juvenescence

PLoS One. 2021 Apr 22;16(4):e0248517. doi: 10.1371/journal.pone.0248517. eCollection 2021.

Authors

Takao Morimune^{1

2

3}, Ayami Tano^{1

3}, Yuya Tanaka^{1

3}, Haruka Yukiue¹, Takefumi Yamamoto⁴, Ikuo Tooyama¹, Yoshihiro Maruo², Masaki Nishimura¹, Masaki Mori^{1

3}

Affiliations

¹ Molecular Neuroscience Research Center (MNRC), Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, Japan.
² Department of Pediatrics, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, Japan.
³ Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
⁴ Central Research Laboratory, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, Japan.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / cytology
Brain / metabolism*
Cell Line
Cells, Cultured
GTPase-Activating Proteins / genetics
GTPase-Activating Proteins / metabolism*
Gene Expression Regulation
Humans
Mice
Mice, Inbred C57BL
Neurons / cytology
Neurons / metabolism*
RNA, Long Noncoding / genetics
RNA, Long Noncoding / metabolism*

Substances

GTPase-Activating Proteins
RNA, Long Noncoding
Tbc1d24 protein, mouse

Grants and funding

T.M. is supported by a research grant from the Morinaga Service Society. M.M. is supported by research grants from the Kato Memorial Bioscience Foundation, the Japan Epilepsy Research Foundation (JERF), the Hoansha Foundation, MSD Life Science Foundation, the Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care, Japan Brain Foundation, Takeda Science Foundation and the Japan Spina Bifida & Hydrocephalus Research Foundation. This study was supported by Grants-in-Aid for Scientific Research for Young Scientists from the Japan Intractable Diseases (Nanbyo) Research Foundation. This study was supported by JSPS KAKENHI Grant Numbers 15H01486, 18K07788 and 19H04774, the Leading Initiative for Excellent Young Researchers (LEADER) 5013323 and the Initiative on Rare and Undiagnosed Diseases (IRUD) of AMED. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.