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

Although it is well established that the protein α-synuclein (αS) 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 αS 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 αS in membrane remodeling we investigated the number of αS proteins associated with single small vesicles in a neuronal cell model. Using single-molecule microscopy and photo-bleaching approaches, we most frequently found 70 αS-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 αS, per vesicle. We therefore hypothesize a dual synergistic role for αS in membrane remodeling acting both as a modulator of the membrane’s physical properties and interaction partner for synaptobrevin.