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

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, pro...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9eaa40d0e3454fffa98e5440007fc225
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spelling	oai:doaj.org-article:9eaa40d0e3454fffa98e5440007fc2252021-12-02T16:06:07ZSphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion10.1038/s41598-017-05948-z2045-2322https://doaj.org/article/9eaa40d0e3454fffa98e5440007fc2252017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05948-zhttps://doaj.org/toc/2045-2322Abstract 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.Frederic D. DariosJernej JorgacevskiAjda FlaškerRobert ZorecVirginia García-MartinezJosé VillanuevaLuis M. GutiérrezCharlotte LeeseManjot BalElena NosyrevaEge T. KavalaliBazbek DavletovNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion
description	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.
format	article
author	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
author_facet	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
author_sort	Frederic D. Darios
title	Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion
title_short	Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion
title_full	Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion
title_fullStr	Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion
title_full_unstemmed	Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion
title_sort	sphingomimetic multiple sclerosis drug fty720 activates vesicular synaptobrevin and augments neuroendocrine secretion
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9eaa40d0e3454fffa98e5440007fc225
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Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion

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