Mammalian ribosomal and chaperone protein RPS3A counteracts alpha-Synuclein aggregation and toxicity in a yeast model system

Accumulation of aggregated forms of alpha-synuclein (αSyn) into Lewy bodies is a known hallmark associated with neuronal cell death in Parkinson’s disease. When expressed in the yeast Saccharomyces cerevisiae, αSyn interacts with the plasma membrane, forms inclusions and causes a concentration-dependent growth defect. We have used a yeast mutant, cog6Δ, which is particularly sensitive to moderate αSyn expression, for screening a mouse brain-specific cDNA library in order to identify mammalian proteins that counteract αSyn toxicity. The mouse ribosomal and chaperone protein RPS3A was identified as a suppressor of αSyn (WT 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 αSyn-induced growth defect, illustrating the potential of our screening system to identify modifiers that would be missed using yeast gene overexpression as first screening step. Co-expression of mouse RPS3A delayed the formation of αSyn-GFP inclusions in the yeast cells. Our results suggest that the recently identified extraribosomal chaperonin function of RPS3A also acts on the neurodegeneration-related protein αSyn and reveal a new avenue for identifying promising candidate mammalian proteins involved in αSyn functioning.

Source: BJ Cell - August 7, 2013 Category: Biochemistry Authors: S De Graeve, S Marinelli, F Stolz, J Hendrickx, J Vandamme, Y Engelborghs, P Van Dijck, J M. Thevelein Tags: BJ Disease Source Type: research