A method to quantitatively measure the proteostasis capacity of cells

Protein homeostasis, or proteostasis, refers to the maintenance of the conformational and functional integrity of the proteome. The term proteostasis therefore encompasses all of the pathways that regulate the synthesis, concentration, folding, trafficking and degradation of proteins. The proteostasis capacity of a cell can be defined as the ability to prevent protein accumulation and aggregation into intracellular inclusions. Thus, proteostasis capacity is highly dependent on the protein quality control network. The ability to quantitatively measure the proteostasis capacity of a cell is an important step towards deciphering why some cell types are more susceptible to the formation of inclusions than others. This work demonstrates that FlucDM forms inclusions more readily in NSC-34 cells compared to Neuro-2a cells. The inclusions formed by FlucDM 94 in both Neuro-2a and NSC-34 cells were purified in order to identify differences in the types of proteins that engage with aggregation prone proteins in these cells. Overall, this work represents a first step towardsusing a model aggregation-prone protein to quantitatively measure the proteostasis capacity of cells, and thus understanding why some cells are vulnerable to proteome dysfunction, leading to the formation of inclusions.