| First Author | De Graeve S | Year | 2013 |
| Journal | Biochem J | Volume | 455 |
| Issue | 3 | Pages | 295-306 |
| PubMed ID | 23924367 | Mgi Jnum | J:202694 |
| Mgi Id | MGI:5521240 | Doi | 10.1042/BJ20130417 |
| Citation | De Graeve S, et al. (2013) Mammalian ribosomal and chaperone protein RPS3A counteracts alpha-synuclein aggregation and toxicity in a yeast model system. Biochem J 455(3):295-306 |
| abstractText | Accumulation of aggregated forms of alphaSyn (alpha-synuclein) into Lewy bodies is a known hallmark associated with neuronal cell death in Parkinson's disease. When expressed in the yeast Saccharomyces cerevisiae, alphaSyn interacts with the plasma membrane, forms inclusions and causes a concentration-dependent growth defect. We have used a yeast mutant, cog6Delta, which is particularly sensitive to moderate alphaSyn expression, for screening a mouse brain-specific cDNA library in order to identify mammalian proteins that counteract alphaSyn toxicity. The mouse ribosomal and chaperone protein RPS3A was identified as a suppressor of alphaSyn [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 alphaSyn-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 alphaSyn-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 alphaSyn and reveal a new avenue for identifying promising candidate mammalian proteins involved in alphaSyn functioning. |
