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StAR-related lipid transfer domain 11 (STARD11)–mediated ceramide transport mediates extracellular vesicle biogenesis


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Title: StAR-related lipid transfer domain 11 (STARD11)–mediated ceramide transport mediates extracellular vesicle biogenesis
Other Titles: 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
Authors: 福島, 真典
Authors (alternative): Fukushima, Masanori
Issue Date: 19-Mar-2020
Publisher: American Society for Biochemistry and Molecular Biology
Citation: Nagasaki University (長崎大学), 博士(医学) (2020-03-19)
Abstract: 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.
Description: 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 / Author: Masanori Fukushima, Debanjali Dasgupta, Amy S. Mauer, Eiji Kakazu, Kazuhiko Nakao and Harmeet Malhi / Citation: The Journal of Biological Chemistry, 293(39), pp.15277-15289; 2018
URI: http://hdl.handle.net/10069/39734
ISSN: 00219258
DOI: 10.1074/jbc.RA118.002587
Rights: © 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
Type: Thesis or Dissertation
Text Version: ETD
Appears in Collections:dissertation

Citable URI : http://hdl.handle.net/10069/39734

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