α-Synuclein Can Inhibit SNARE-Mediated Vesicle Fusion through Direct Interactions with Lipid Bilayers

The native function of alpha-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 alpha-synuclein inhibits SNARE-mediated vesicle fusion through binding the membrane, without a direct interaction between alpha-synuclein and any of the SNARE proteins. This work supports a model in which alpha-synuclein plays a role in the regulation of vesicle fusion by modulating properties of the lipid bilayer.