Clearance of protein aggregates by exophers (C10*)

exophers 清除蛋白质聚集体 (C10*)

• 批准号: 436150538
• 金额: --
• 依托单位: Arbeitsgruppe Molekulare Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2020
• 资助国家: 德国
• 起止时间: 2019-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/436150538?language=en
• 关键词: Clearance; protein; aggregates; exophers; C10

This project investigates the function of a recently described quality control secretion pathway in which toxic protein aggregates and damaged organelles are released from cells in a large extracellular vesicle called exopher. The molecular mechanisms of exopher production that involve targeting, sequestration, and finally the secretion of proteotoxic substances in a plasma membrane-surrounded vesicle are unknown. We will perform a genome-wide unbiased RNAi screen in a C. elegans exopher model to elucidate the molecular players in the exopher pathway. Furthermore, we will investigate isolated exophers by biophysical and biochemical methods in order to identify a specific exopher signature. A further aim of this project is to investigate the role of molecular chaperones including the HSP70 system in the exopher targeting and sequestration process of aggregation-prone proteins.

这个项目研究了最近描述的一种质量控制分泌途径的功能，在这种途径中，有毒的蛋白质聚集体和受损的细胞器从称为Exopher的大型细胞外小泡中释放出来。外液产生的分子机制涉及靶向、隔离，最后在质膜包围的小泡中分泌蛋白毒性物质，目前尚不清楚。我们将在线虫外显子模型中进行全基因组无偏RNAi筛选，以阐明外显子途径中的分子参与者。此外，我们将通过生物物理和生化方法对分离的外显色体进行研究，以确定特定的外显色体特征。该项目的另一个目的是研究包括HSP70系统在内的分子伴侣在易于聚集的蛋白质的外膜靶向和隔离过程中的作用。