Parkinson's disease is the most common neurodegenerative movement disorder. 
α-Synuclein is a small synaptic protein that has been linked to familial 
Parkinson's disease (PD) and is also the primary component of Lewy bodies, the 
hallmark neuropathology found in the brain of sporadic and familial PD patients. 
The function of α-synuclein is currently unknown, although it has been 
implicated in the regulation of synaptic vesicle localization or fusion. 
Recently, overexpression of α-synuclein was shown to cause cytoplasmic vesicle 
accumulation in a yeast model of α-synuclein toxicity, but the exact role 
α-synuclein played in mediating this vesicle aggregation is unclear. Here, we 
show that α-synuclein induces aggregation of many yeast Rab GTPase proteins, 
that α-synuclein aggregation is enhanced in yeast mutants that produce high 
levels of acidic phospholipids, and that α-synuclein colocalizes with yeast 
membranes that are enriched for phosphatidic acid. Significantly, we demonstrate 
that α-synuclein expression induces vulnerability to perturbations of Ypt6 and 
other proteins involved in retrograde endosome-Golgi transport, linking a 
specific trafficking defect to α-synuclein phospholipid binding. These data 
suggest new pathogenic mechanisms for α-synuclein neurotoxicity.