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α‐Synuclein sequesters arachidonic acid to modulate SNARE‐mediated exocytosis
Author(s) -
Darios Frédéric,
Ruipérez Violeta,
López Inmaculada,
Villanueva Jose,
Gutierrez Luis M,
Davletov Bazbek
Publication year - 2010
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2010.66
Subject(s) - exocytosis , arachidonic acid , microbiology and biotechnology , snare complex , neurotransmission , biology , munc 18 , cytosol , synaptic vesicle , synuclein , snap25 , lipid bilayer fusion , biochemistry , alpha synuclein , receptor , vesicle , secretion , parkinson's disease , medicine , disease , pathology , membrane , enzyme
α‐Synuclein is a synaptic modulatory protein implicated in the pathogenesis of Parkinson disease. The precise functions of this small cytosolic protein are still under investigation. α‐Synuclein has been proposed to regulate soluble N ‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) proteins involved in vesicle fusion. Interestingly, α‐synuclein fails to interact with SNARE proteins in conventional protein‐binding assays, thus suggesting an indirect mode of action. As the structural and functional properties of both α‐synuclein and the SNARE proteins can be modified by arachidonic acid, a common lipid regulator, we analysed this possible tripartite link in detail. Here, we show that the ability of arachidonic acid to stimulate SNARE complex formation and exocytosis can be controlled by α‐synuclein, both in vitro and in vivo . α‐Synuclein sequesters arachidonic acid and thereby blocks the activation of SNAREs. Our data provide mechanistic insights into the action of α‐synuclein in the modulation of neurotransmission.