Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion

Frederic D. Darios, Jernej Jorgacevski, Ajda Flašker, Robert Zorec, Virginia García-Martinez, José Villanueva, Luis M. Gutiérrez, Charlotte Leese, Manjot Bal, Elena Nosyreva, Ege T. Kavalali, Bazbek Davletov

Research output: Contribution to journalArticle

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Abstract

Neurotransmission and secretion of hormones involve a sequence of protein/lipid interactions with lipid turnover impacting on vesicle trafficking and ultimately fusion of secretory vesicles with the plasma membrane. We previously demonstrated that sphingosine, a sphingolipid metabolite, promotes formation of the SNARE complex required for membrane fusion and also increases the rate of exocytosis in isolated nerve terminals, neuromuscular junctions, neuroendocrine cells and in hippocampal neurons. Recently a fungi-derived sphingosine homologue, FTY720, has been approved for treatment of multiple sclerosis. In its non-phosphorylated form FTY720 accumulates in the central nervous system, reaching high levels which could affect neuronal function. Considering close structural similarity of sphingosine and FTY720 we investigated whether FTY720 has an effect on regulated exocytosis. Our data demonstrate that FTY720 can activate vesicular synaptobrevin for SNARE complex formation and enhance exocytosis in neuroendocrine cells and neurons.

Original languageEnglish (US)
Article number5958
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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R-SNARE Proteins
Multiple Sclerosis
Sphingosine
Exocytosis
SNARE Proteins
Neuroendocrine Cells
Pharmaceutical Preparations
Lipids
Neurons
Sphingolipids
Membrane Fusion
Neuromuscular Junction
Secretory Vesicles
Synaptic Transmission
Fungi
Central Nervous System
Cell Membrane
Fingolimod Hydrochloride
Hormones
Proteins

ASJC Scopus subject areas

  • General

Cite this

Darios, F. D., Jorgacevski, J., Flašker, A., Zorec, R., García-Martinez, V., Villanueva, J., ... Davletov, B. (2017). Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion. Scientific Reports, 7(1), [5958]. https://doi.org/10.1038/s41598-017-05948-z

Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion. / Darios, Frederic D.; Jorgacevski, Jernej; Flašker, Ajda; Zorec, Robert; García-Martinez, Virginia; Villanueva, José; Gutiérrez, Luis M.; Leese, Charlotte; Bal, Manjot; Nosyreva, Elena; Kavalali, Ege T.; Davletov, Bazbek.

In: Scientific Reports, Vol. 7, No. 1, 5958, 01.12.2017.

Research output: Contribution to journalArticle

Darios, FD, Jorgacevski, J, Flašker, A, Zorec, R, García-Martinez, V, Villanueva, J, Gutiérrez, LM, Leese, C, Bal, M, Nosyreva, E, Kavalali, ET & Davletov, B 2017, 'Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion', Scientific Reports, vol. 7, no. 1, 5958. https://doi.org/10.1038/s41598-017-05948-z
Darios, Frederic D. ; Jorgacevski, Jernej ; Flašker, Ajda ; Zorec, Robert ; García-Martinez, Virginia ; Villanueva, José ; Gutiérrez, Luis M. ; Leese, Charlotte ; Bal, Manjot ; Nosyreva, Elena ; Kavalali, Ege T. ; Davletov, Bazbek. / Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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