Secretory protein folding, modification and the unfolded protein response

The endoplasmic reticulum (ER) is the gateway for proteins to exit cells and plays a key role in ensuring only functional proteins are secreted. Several enzymes and molecular chaperones are located in this organelle with the specific purpose to ensure correct protein folding and to prevent the secretion of misfolded proteins. Breakdown of this folding and quality control system leads to diseases such as diabetes, neurodegeneration and cancer. Here we aim to understand the fundamental processes involved when proteins enter the ER, how the cell maintains the correct environment for folding as well as how the cell responds to stress. We reconstitute some of the processes using isolated components which allows us to dissect the sequence of events following entry of proteins into the ER. A greater understanding of the early stages of the secretory pathway informs the underlying causes of disease as well as potential new therapeutics.