The Localization of Alpha-synuclein in the Endocytic Pathway

Alpha-synuclein (?S) is an intrinsically disordered protein (IDP) that abundantly present in the brain and associated with Parkinson's disease (PD). In spite of its abundance contribution to PD pathogenesis, exact cellular function ?S remains largely unknown. The ability remodel phospholipid model membranes combined biochemical studies suggests involved endocytosis. To unravel which route(s) stage(s) endocytic pathway associated, we quantified colocalization between marker proteins differentiated SH-SY5Y neuronal cells, using object based analysis. Comparison randomized data allowed us discriminate structural coincidental colocalizations. A large fraction positive vesicles colocalizes caveolin vesicles, a smaller EEA1 Rab7. We find no clathrin Rab11 vesicles. conclude physiological context, structurally dependent membrane vesiculation found further along pathway, decreasing amounts, on early late endosomes. Our results not only shed new light ?S, they also provide possible link vesicle trafficking malfunction PD.