Protein accumulation represents the consequence of an altered cellular homeostasis leading to an imbalance between synthesis and disposal. Cells adopt a number of strategies to cope with this imbalance: through the Unfolded Protein Response (UPR), intracellular chaperons are increased to facilitate protein folding, and the Endoplasmic Reticulum (ER) expands to accommodate increased concentration of ER resident proteins. The induction of autophagy is also a strategy adopted to face the synthesis of aberrant proteins. Our cellular model of protein accumulation regards mutant immunoglobulin: Ig-µ chain that lacks the first constant domain (µ∆CH1 chain). These aberrant chains can neither exit from, nor are efficiently degraded in the ER. As a consequence they accumulate generating dilated cisternae known as Russell bodies. Russell bodies are frequently detected in lymphoproliferative diseases, especially in disorders of secretory B cells. Condensation of aberrant µ∆CH1 chains can occur in different sub-cellular locations: when Ig-L chains are produced detergent insoluble aggregates form in the rough ER; without L chains, aggregation occurs in ERGIC compartment. We are interested to define whether and which cellular mechanisms are active or are impaired by the synthesis of aberrant Ig-µ chains assaying: i.e. ER stress, ER expansion, Autophagy modulation in our inducible cellular model (Hela-tet off) of Russell bodies formation. Our aim is to define if Russell bodies structures are a cell defence mechanism against proteotoxicity
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