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

Masanori Fukushima, Debanjali Dasgupta, Amy S. Mauer, Eiji Kakazu, Kazuhiko Nakao, Harmeet M Malhi

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.Wefurther 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, andmultivesicular 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.

Original languageEnglish (US)
Pages (from-to)15277-15289
Number of pages13
JournalJournal of Biological Chemistry
Volume293
Issue number39
DOIs
StatePublished - Jan 1 2018

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Ceramides
Lipids
Palmitates
Exosomes
Multivesicular Bodies
Endoplasmic Reticulum
Cells
Extracellular Vesicles
Biosynthesis
Cell Communication
Liver
Machinery
Hepatocytes
Carrier Proteins
Health
Association reactions
Cell Line

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

StAR-related lipid transfer domain 11 (STARD11)-mediated ceramide transport mediates extracellular vesicle biogenesis. / Fukushima, Masanori; Dasgupta, Debanjali; Mauer, Amy S.; Kakazu, Eiji; Nakao, Kazuhiko; Malhi, Harmeet M.

In: Journal of Biological Chemistry, Vol. 293, No. 39, 01.01.2018, p. 15277-15289.

Research output: Contribution to journalArticle

Fukushima, Masanori ; Dasgupta, Debanjali ; Mauer, Amy S. ; Kakazu, Eiji ; Nakao, Kazuhiko ; Malhi, Harmeet M. / StAR-related lipid transfer domain 11 (STARD11)-mediated ceramide transport mediates extracellular vesicle biogenesis. In: Journal of Biological Chemistry. 2018 ; Vol. 293, No. 39. pp. 15277-15289.
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