Sphingosine Facilitates SNARE Complex Assembly and Activates Synaptic Vesicle Exocytosis

Frédéric Darios, Catherine Wasser, Anastasia Shakirzyanova, Artur Giniatullin, Kerry Goodman, Jose L. Munoz-Bravo, Jesica Raingo, Jernej Jorgačevski, Marko Kreft, Robert Zorec, Juliana M. Rosa, Luis Gandia, Luis M. Gutiérrez, Thomas Binz, Rashid Giniatullin, Ege T. Kavalali, Bazbek Davletov

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Synaptic vesicles loaded with neurotransmitters fuse with the plasma membrane to release their content into the extracellular space, thereby allowing neuronal communication. The membrane fusion process is mediated by a conserved set of SNARE proteins: vesicular synaptobrevin and plasma membrane syntaxin and SNAP-25. Recent data suggest that the fusion process may be subject to regulation by local lipid metabolism. Here, we have performed a screen of lipid compounds to identify positive regulators of vesicular synaptobrevin. We show that sphingosine, a releasable backbone of sphingolipids, activates synaptobrevin in synaptic vesicles to form the SNARE complex implicated in membrane fusion. Consistent with the role of synaptobrevin in vesicle fusion, sphingosine upregulated exocytosis in isolated nerve terminals, neuromuscular junctions, neuroendocrine cells and hippocampal neurons, but not in neurons obtained from synaptobrevin-2 knockout mice. Further mechanistic insights suggest that sphingosine acts on the synaptobrevin/phospholipid interface, defining a novel function for this important lipid regulator.

Original languageEnglish (US)
Pages (from-to)683-694
Number of pages12
JournalNeuron
Volume62
Issue number5
DOIs
Publication statusPublished - Jun 11 2009

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Keywords

  • CELLBIO
  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Darios, F., Wasser, C., Shakirzyanova, A., Giniatullin, A., Goodman, K., Munoz-Bravo, J. L., ... Davletov, B. (2009). Sphingosine Facilitates SNARE Complex Assembly and Activates Synaptic Vesicle Exocytosis. Neuron, 62(5), 683-694. https://doi.org/10.1016/j.neuron.2009.04.024