Characterization of the Role in Parkinson's Disease of the Rab1 GTPase, a Master Regulator of the Endomembrane System

We aim to analyze the effect of a-synuclein and its aggregates on defined functional features of Rab1.

We propose that Rab1 recruits downstream effectors that are essential transport machinery proteins and regulates the employment of cellular energy sources to sustain large fluxes of trafficked cargo proteins and membranes.
 

We propose that the level of downstream effectors recruitment is determined by Rab1-cargo interaction. We will test the hypothesis that a-synuclein may interfere with Rab1-cargo interaction and, in so doing, disrupts the extensive trafficking required for dopaminergic neurons maintenance and function in the Substantia Nigra (SN).