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StAR-related lipid transfer domain 11 (STARD11)-mediated ceramide transport mediates extracellular vesicle biogenesis
http://hdl.handle.net/10069/39734
http://hdl.handle.net/10069/39734476da4d4-655d-4c9b-b69d-e932dd3e28d7
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
ISYK1222_Fukushima.pdf (4.3 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2020-03-26 | |||||
| タイトル | ||||||
| タイトル | StAR-related lipid transfer domain 11 (STARD11)-mediated ceramide transport mediates extracellular vesicle biogenesis | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| 著者 |
福島, 真典
× 福島, 真典 |
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| 著者別名 | ||||||
| 識別子Scheme | WEKO | |||||
| 識別子 | 116656 | |||||
| 姓名 | Fukushima, Masanori | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Extracellular vesicles are important carriers of cellular materials and have critical roles in cell-to-cell communication in both health and disease. Ceramides are implicated in extracellular vesicle biogenesis, yet the cellular machinery that mediates the formation of ceramide-enriched extracellular vesicles remains unknown. We demonstrate here that the ceramide transport protein StAR-related lipid transfer domain 11 (STARD11) mediates the release of palmitate-stimulated extracellular vesicles having features consistent with exosomes. Using palmitate as a model of lipotoxic diseases and as a substrate for ceramide biosynthesis in human and murine liver cell lines and primary mouse hepatocytes, we found that STARD11-deficient cells release fewer extracellular vesicles. Moreover, STARD11 reciprocally regulated exosome ceramide enrichment and cellular ceramide depletion. We further observed that in STARD11 knockout cells intracellular ceramide accumulates and that this apparent inability to transfer cellular ceramide into extracellular vesicles reduces cellular viability. Using endogenous markers, we uncovered structural and functional colocalization of the endoplasmic reticulum (ER), STARD11, and multivesicular bodies. This colocalization increased following palmitate treatment, suggesting a functional association that may mediate ceramide trafficking from the ER to the multivesicular body. However, the size and number of multivesicular bodies were comparable in WT and STARD11-knockout cells. In conclusion, we propose a model of how STARD11 mediates ceramide trafficking in palmitate-treated cells and stimulates exosome biogenesis. | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 長崎大学学位論文 学位記番号:博(医歯薬)甲第1222号 学位授与年月日:令和2年3月19日 | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Author: Masanori Fukushima, Debanjali Dasgupta, Amy S. Mauer, Eiji Kakazu, Kazuhiko Nakao and Harmeet Malhi | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Citation: The Journal of Biological Chemistry, 293(39), pp.15277-15289; 2018 | |||||
| 書誌情報 |
The Journal of Biological Chemistry 巻 293, 号 39, p. 15277-15289, 発行日 2020-03-19 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 00219258 | |||||
| EISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1083351X | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1074/jbc.RA118.002587 | |||||
| 権利 | ||||||
| 権利情報 | c 2018 Fukushima et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc. This research was originally published in the Journal of Biological Chemistry, 293(39), pp.15277-15289; 2018 |
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| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| その他のタイトル | ||||||
| その他のタイトル | StAR関連脂質輸送ドメイン11(STARD11)媒介セラミド輸送は細胞外小胞合成に関与する | |||||
| 出版者 | ||||||
| 出版者 | American Society for Biochemistry and Molecular Biology | |||||
| 関係URI | ||||||
| 識別子タイプ | HDL | |||||
| 関連識別子 | http://hdl.handle.net/10069/39920 | |||||
| 学位名 | ||||||
| 学位名 | 博士(医学) | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 17301 | |||||
| 学位授与機関名 | Nagasaki University (長崎大学) | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2020-03-19 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲医歯薬第1222号 | |||||
| 学位の種類 | ||||||
| 値 | 課程博士 | |||||
| 引用 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Nagasaki University (長崎大学), 博士(医学) (2020-03-19) | |||||
