The Interaction between Rab3a and α-Synuclein, and its Implications on α-Synuclein Membrane-binding

α-Synuclein is an abundant nerve terminal protein and a primary component of the Lewy body pathology seen in Parkinson’s disease. While the precise biological and pathological role of α-synuclein remains unclear, its ability to bind to and dissociate from synaptic membranes may be linked to its function in these states. In this thesis, we characterized the role of the GTPase protein rab3a as a potential regulator of α-synuclein membrane binding and dissociation. We found evidence that GTP-bound rab3a sequesters α-synuclein on membranes during exocytosis, and that inhibition of rab3a dissociation from the membrane causes inhibition of α-synuclein dissociation as well. Furthermore, we found that the loss of rab3a in human neuroblastoma cells increases α-synuclein expression. This study identifies rab3a and proteins associated with its membrane dissociation as mediators of α-synuclein membrane binding and dissociation.MAS