The number of α-synuclein proteins per vesicle gives insights into its physiological function

Although it is well established that the protein alpha-synuclein (alpha S) plays an important role in Parkinson's disease, its physiological function remains largely unknown. It has been reported to bind membranes and to play a role in membrane remodeling processes. The mechanism by which alpha S remodels membranes is still debated; it may either affect its physical properties or act as a chaperone for other membrane associated proteins. To obtain insight into the role of alpha S in membrane remodeling we investigated the number of alpha S proteins associated with single small vesicles in a neuronal cell model. Using single-molecule microscopy and photo-bleaching approaches, we most frequently found 70 alpha S-GFPs per vesicle. Although this number is high enough to modulate physical membrane properties, it is also strikingly similar to the number of synaptobrevins, a putative interaction partner of alpha S, per vesicle. We therefore hypothesize a dual, synergistic role for alpha S in membrane remodeling.