Exploration of Glucosylceramide Transport Factors Using CRISPR Library
| Project/Area Number |
17K07357
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | スフィンゴ糖脂質 / ゲノム編集 / スクリーニング / ゴルジ体 / 糖脂質 / ゲノムワイドスクリーニング / 脂質輸送 / 糖鎖 / 脂質 / 膜輸送 |
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| Outline of Final Research Achievements |
In this study, we used CRISPR knockout library to search for novel factors affecting glycolipid transport. We succeeded in identifying genes involved in glycolipid metabolisms with high coverage. We succeeded in identifying SYS1, a multi-spanning transmembrane protein localized in the Golgi apparatus, in Vero cells. Knockout of SYS1 gene reduced Gb3 and instead remarkably increased GlcCer. The SYS1 knockout cells also showed a change in the morphology of the Golgi apparatus from an elongated laminar to an aggregated form, and dot-like structures of a trans-Golgi network marker TGN46 around the Golgi apparatus. This indicates that SYS1 regulates glycan biosynthesis through its involvement in the Golgi apparatus and trans-Golgi network trafficking.
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| Academic Significance and Societal Importance of the Research Achievements |
スフィンゴ糖脂質は、高次機能や疾患に深く関与することが知られており、生体に欠かせない脂質である。スフィンゴ糖脂質の生合成酵素はほぼ同定されているものの、細胞内輸送因子に関しては未解明な点が残されており、代謝・輸送に関する因子の同定は重要な課題である。本研究により、ゴルジ体における糖鎖生合成の制御に関して重要な知見を得ており、糖鎖生物学及び細胞生物学的分野における学術的意義を示すものである。
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Report
(6 results)
Research Products
(37 results)
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[Journal Article] Golgi maturation-dependent glycoenzyme recycling controls glycosphingolipid biosynthesis and cell growth via GOLPH3.2021
Author(s)
Riccardo Rizzo, Domenico Russo, Kazuo Kurokawa, Alfredo Budillon, Franck Perez, Seetharaman Parashuraman, Yusuf A Hannun, Akihiko Nakano, Daniela Corda, Giovanni D’Angelo and Alberto Luini et al.,.
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Journal Title
The EMBO Journal
Volume: 40
Issue: 8
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Sphingomyelin Is Essential for the Structure and Function of the Double-Membrane Vesicles in Hepatitis C Virus RNA Replication Factories2020
Author(s)
Gewaid H, Aoyagi H, Arita M, Watashi K, Suzuki R, Sakai S, Kumagai K, Yamaji T, Fukasawa M, Kato F, Hishiki T, Mimata A, Sakamaki Y, Ichinose S, Hanada K, Muramatsu M, Wakita T, Aizaki H.
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Journal Title
J Virol
Volume: 94
Issue: 23
DOI
Related Report
Peer Reviewed
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[Journal Article] Nanotubes connecting B lymphocytes: High impact of differentiation-dependent lipid composition on their growth and mechanics2017
Author(s)
Toth EA, Oszvald A, Peter M, Balogh G, Osteikoetxea- Molnar A, Bozo T, Szabo-Meleg E, Nyitrai M, Derenyi I, Yamaji T, Hanada K, Vigh L, Matko J
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Journal Title
Biochimica et Biophysica Acta
Volume: 1862
Issue: 9
Pages: 991-1000
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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