Clearance of protein aggregates by exophers (C10*)

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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.