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Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion.
Darios, Frederic D; Jorgacevski, Jernej; Flasker, Ajda; Zorec, Robert; García-Martinez, Virginia; Villanueva, José; Gutiérrez, Luis M; Leese, Charlotte; Bal, Manjot; Nosyreva, Elena; Kavalali, Ege T; Davletov, Bazbek.
Afiliación
  • Darios FD; MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.
  • Jorgacevski J; Hôpital Pitié Salpêtrière, ICM, 75013, Paris, France.
  • Flasker A; Laboratory of Neuroendocrinology-Molecular Cell Physiology, Faculty of Medicine, University of Ljubljana, 1000, Ljubljana, Slovenia.
  • Zorec R; Celica Biomedical, 1000, Ljubljana, Slovenia.
  • García-Martinez V; Laboratory of Neuroendocrinology-Molecular Cell Physiology, Faculty of Medicine, University of Ljubljana, 1000, Ljubljana, Slovenia.
  • Villanueva J; Laboratory of Neuroendocrinology-Molecular Cell Physiology, Faculty of Medicine, University of Ljubljana, 1000, Ljubljana, Slovenia.
  • Gutiérrez LM; Celica Biomedical, 1000, Ljubljana, Slovenia.
  • Leese C; Institute of Neurosciences, CSIC-Miguel Hernandez University, 03550, Alicante, Spain.
  • Bal M; Institute of Neurosciences, CSIC-Miguel Hernandez University, 03550, Alicante, Spain.
  • Nosyreva E; Institute of Neurosciences, CSIC-Miguel Hernandez University, 03550, Alicante, Spain.
  • Kavalali ET; Department of Biomedical Sciences, University of Sheffield, Sheffield, S10 2TN, UK.
  • Davletov B; Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
Sci Rep ; 7(1): 5958, 2017 07 20.
Article en En | MEDLINE | ID: mdl-28729700
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esfingosina / Vesículas Sinápticas / Proteínas R-SNARE / Clorhidrato de Fingolimod / Esclerosis Múltiple / Sistemas Neurosecretores Límite: Animals Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esfingosina / Vesículas Sinápticas / Proteínas R-SNARE / Clorhidrato de Fingolimod / Esclerosis Múltiple / Sistemas Neurosecretores Límite: Animals Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article Pais de publicación: Reino Unido