Ataxin-1 fusion partners alter polyQ lethality and aggregation.

摘要: Intranuclear inclusion bodies (IBs) are the histopathologic markers of multiple protein folding diseases. IB formation has been extensively studied using fluorescent fusion products pathogenic polyglutamine (polyQ) expressing proteins. These studies have informative in determining cellular targets expanded polyQ as well methods by which cells rid themselves IBs. The experimental thrust to intervene process aggregation an attempt alleviate cytotoxicity. However new data argues against notion that and cytotoxicity inextricably linked processes. We reasoned changing context a disease causing could accelerate its precipitation IB, potentially reducing Our strategy simply exploited fact conjoined proteins influence each others properties. fused full-length ataxin-1 construct tags (GFP DsRed1-E5) exist at different oligomeric states. spectral properties DsRed1-E5-ataxin-1 transfectants had additional advantage allowing us correlate fluorochrome maturation with Each expressed distinct morphology. Flow cytometric analyses greatest signals revealed was more toxic than GFP (31.8±4.5% cell death versus 12.85±3%), although co-transfection inhibited DsRed1-E5 diminished toxicity fusion. show driven can be influenced partners generate species provide opportunities study aggregation, lethality.