α-Synuclein can inhibit SNARE-mediated vesicle fusion through direct interactions with lipid bilayers.

The native function of α-synuclein is thought to involve regulation of synaptic vesicle trafficking. Recent work has also implicated a role in neurotransmission, possibly through interactions with the proteins involved in synaptic vesicle fusion. Here, we demonstrate that α-synuclein inhibits SNARE-mediated vesicle fusion through binding the membrane, without a direct interaction between α-synuclein and any of the SNARE proteins. This work supports a model in which α-synuclein plays a role in the regulation of vesicle fusion by modulating properties of the lipid bilayer.