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Reference: De Graeve S, et al. (2013) Mammalian ribosomal and chaperone protein RPS3A counteracts a-synuclein aggregation and toxicity in a yeast model system. Biochem J 455(3):295-306

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Abstract


Accumulation of aggregated forms of aSyn (a-synuclein) into Lewy bodies is a known hallmark associated with neuronal cell death in Parkinson's disease. When expressed in the yeast Saccharomyces cerevisiae, aSyn interacts with the plasma membrane, forms inclusions and causes a concentration-dependent growth defect. We have used a yeast mutant, cog6?, which is particularly sensitive to moderate aSyn expression, for screening a mouse brain-specific cDNA library in order to identify mammalian proteins that counteract aSyn toxicity. The mouse ribosomal and chaperone protein RPS3A was identified as a suppressor of aSyn [WT (wild-type) and A53T] toxicity in yeast. We demonstrated that the 50 N-terminal amino acids are essential for this function. The yeast homologues of RPS3A were not effective in suppressing the aSyn-induced growth defect, illustrating the potential of our screening system to identify modifiers that would be missed using yeast gene overexpression as the first screening step. Co-expression of mouse RPS3A delayed the formation of aSyn-GFP inclusions in the yeast cells. The results of the present study suggest that the recently identified extraribosomal chaperonin function of RPS3A also acts on the neurodegeneration-related protein aSyn and reveal a new avenue for identifying promising candidate mammalian proteins involved in aSyn functioning.

Reference Type
Journal Article
Authors
De Graeve S, Marinelli S, Stolz F, Hendrickx J, Vandamme J, Engelborghs Y, Van Dijck P, Thevelein JM
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