Functional cooperation of α-synuclein and VAMP2 in synaptic vesicle recycling

The function of alpha-synuclein (alpha-syn) has been long debated, and two seemingly divergent views have emerged. In one, alpha-syn binds to VAMP2, acting as a SNARE chaperone-but with no effect on neurotransmission-while another posits that alpha-syn attenuates neurotransmitter release by restricting synaptic vesicle mobilization and recycling. Here, we show that alpha-syn-VAMP2 interactions are necessary for alpha-syn-induced synaptic attenuation. Our data connect divergent views and suggest a unified model of alpha-syn function.