Author/Editor		Darios, Frederick; Wasser, Catherine; Shakirzyanova, Anastasia; Giniatullin, Artur; Goodman, Kerry; Munoz-Bravo, Jose L; Raingo, Jesica; Jorgačevski, Jernej; Kreft, Marko; Zorec, Robert
Title		Sphingosine facilitates SNARE complex assembly and activates synaptic vesicle exocytosis
Type		članek
Source		Neuron
Vol. and No.		Letnik 62
Publication year		2009
Volume		str. 683-94
Language		eng
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: vesicuJar 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, areleasable backbone of sphingolipids, activates synaptobrevin in synaptic vesicles to form the SNARE compJex implicated in membrane fusion. Consistent with the roJe of synaptobrevin in vesicle fusion, sphingosine upregulated exocytosis in isolated nerve terminais, neuromuscular junctions, neuroendocrine celi s 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 anovel function for this important lipid regulator.
Descriptors		SYNAPTIC VESICLES SPHINGOSINE EXOCYTOSIS SPHINGOLIPIDS SYNAPSINS MICE, KNOCKOUT