Yeast Prion Aggregates and Protein Recruitment

描述（由申请人提供）：细胞聚集体的存在是许多神经变性疾病如阿尔茨海默病、亨廷顿病和朊病毒病的标志。最近的研究表明，富含谷氨酰胺的蛋白质定位到聚集体中导致功能丧失，可能是观察到的细胞毒性的原因。细胞聚集体与酵母朊病毒[PSI+]相关，这是SUP 35蛋白质的一种错误折叠的自我永存形式。似乎[PSI+]的存在导致一些佐贺突变体的生长较慢。佐贺复合物的成员与Swi/Snf复合物和srb/介体复合物一起参与染色质重塑和转录的共激活。在此，提出在[PSI+]的存在下，参与染色质重塑的富含谷氨酰胺的蛋白质被募集到聚集体中，这导致其功能丧失。将测试其他酵母朊病毒和朊病毒变异株对佐贺突变体的影响。此外，将鉴定细胞聚集体中发现的蛋白质。在聚集体中发现的蛋白质的鉴定将为朊病毒疾病的病因学提供见解。

DESCRIPTION (provided by applicant): The presence of cellular aggregates is a hallmark of many neurodegenerative diseases like Alzheimer's Disease, Huntington's Disease and Prion diseases. Recent studies have revealed that the localization of glutamine-rich proteins into aggregates leads to a loss-of-function and is likely the reason for the observed cell toxicity. Cellular aggregates have been associated with the yeast prion [PSI+], a misfolded self-perpetuating form of the SUP35 protein. It appears that the presence of [PSI+] leads to slower growth in some SAGA mutants. Members of the SAGA complex, in conjunction with the Swi/Snf complex and the srb/mediator complex, are involved in chromatin remodeling and co-activation of transcription. Here, it is proposed that in the presence of [PSI+], glutamine rich proteins involved in chromatin remodeling are being recruited to aggregates, which leads to a loss of their function. The effects other yeast prions and variant strains of prions have on SAGA mutants will be tested. In addition, proteins found within cellular aggregates will be identified. The identification of proteins found within aggregate will provide insight to etiology of prion diseases.