Title: Mammalian ribosomal and chaperone protein RPS3A counteracts α-synuclein aggregation and toxicity in a yeast model system
Authors: De Graeve, Stijn
Marinelli, Sarah
Stolz, Frank
Hendrix, Jelle
Vandamme, Jurgen
Engelborghs, Yves
Van Dijck, Patrick
Thevelein, Johan # ×
Issue Date: Nov-2013
Publisher: Published by Portland Press on behalf of the Biochemical Society
Series Title: Biochemical Journal vol:455 issue:3 pages:295-306
Abstract: Accumulation of aggregated forms of αSyn (α-synuclein) 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 (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 αSyn-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 αSyn-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 αSyn and reveal a new avenue for identifying promising candidate mammalian proteins involved in αSyn functioning.
ISSN: 0264-6021
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Imaging and Photonics
Biochemistry, Molecular and Structural Biology Section
Molecular Microbiology and Biotechnology Section - miscellaneous (-)
× corresponding author
# (joint) last author

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