RGD Reference Report - Alpha-synuclein sequesters arachidonic acid to modulate SNARE-mediated exocytosis. - Rat Genome Database

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Alpha-synuclein sequesters arachidonic acid to modulate SNARE-mediated exocytosis.

Authors: Darios, F  Ruiperez, V  Lopez, I  Villanueva, J  Gutierrez, LM  Davletov, B 
Citation: Darios F, etal., EMBO Rep. 2010 Jul;11(7):528-33. doi: 10.1038/embor.2010.66. Epub 2010 May 21.
RGD ID: 8553846
Pubmed: PMID:20489724   (View Abstract at PubMed)
PMCID: PMC2897113   (View Article at PubMed Central)
DOI: DOI:10.1038/embor.2010.66   (Journal Full-text)

Alpha-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. alpha-Synuclein has been proposed to regulate soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins involved in vesicle fusion. Interestingly, alpha-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 alpha-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 alpha-synuclein, both in vitro and in vivo. Alpha-synuclein sequesters arachidonic acid and thereby blocks the activation of SNAREs. Our data provide mechanistic insights into the action of alpha-synuclein in the modulation of neurotransmission.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:P328518553846PMID:20489724IntAct 
protein binding enablesIPIUniProtKB:P608818553846PMID:20489724IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Snap25  (synaptosome associated protein 25)
Stx1a  (syntaxin 1A)


Additional Information