Figure 1.
A model for α-syn as a regulator of vesicle priming. a, In the presence of wild-type levels of α-syn, vesicles dock with the plasma membrane but are not yet fusion competent (unprimed pool) until primed (releasable pool). α-Syn functions as a regulator of this priming step (green arrow). b, In the presence of high levels of α-syn, vesicles continue to dock with the plasma membrane but now linger in a fusion-incompetent state because of an inhibition of priming. Consequently, the unprimed pool of vesicles increases, and the releasable pool of vesicles decreases, leading to an increase in the number of docked vesicles and a decrease in exocytosis. c, In the absence of α-syn (e.g., mouse knock-out), vesicles dock with the plasma membrane, but priming is dysregulated, leading to excessive priming and a build-up in the releasable pool of primed vesicles, potentially explaining the increased evoked neurotransmitter release observed in neurons from α-syn-deficient mice (Abeliovich et al., 2000).