wildtype α-synuclein, optical density analysis, dilution series spotting, galactose media toxicity, cell lysates
α-Synuclein is implicated in Parkinson’s Disease, a neurodegenerative disease that destroys midbrain neurons. The misfolding and subsequent aggregation of this protein is the likely cause of cell death. A major hypothesis in the field is that increasing α-synuclein’s rate of degradation may prevent its aggregation and toxicity. The prevalent model for α-synuclein degradation is via the proteasome, and malfunctions in this pathway have been shown to increase α-synuclein accumulation and toxicity. However, increasing evidence suggests that the Multivesicular Body (MVB) sorting pathway is involved in protein degradation via the lysosome. To test the role of the MVB sorting pathway for the degradation of wild-type and mutant α-synucleins, we asked if α-synuclein would accumulate and increase toxicity in yeast that lacked one of the MVB proteins. Previously, Price and Shrestha showed that the absence of vps28, an MVB protein caused toxicity in yeast expressing α-synuclein (Eukaryon). We tested another protein, vps34, a PI 3-kinase acting upstream in the proteins involved in the MVB pathway. The absence of vps34 was toxic to yeast and this toxicity was severely exacerbated in the presence of any foreign protein, including α-synuclein. Future research will examine several other essential lysosomal pathway factors in mediating α-synuclein toxicity.
Eukaryon is published by students at Lake Forest College, who are solely responsible for its content. The views expressed in Eukaryon do not necessarily reflect those of the College. Articles published within Eukaryon should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.