ER exit pathways and the control of proteostasis: Crucial role of the UPR, COPII, and ER-phagy in the secretory pathway

The endoplasmic reticulum (ER) is the site of entry of all proteins that function in the secretory pathway including the extracellular environment. Because it controls the folding of newly synthesized secretory proteins, the ER is indispensable for the maintenance of proteostasis in the secretory pathway. Within the ER and, in part, in postER compartments, the quality control of protein folding is under the regulation of the unfolded protein response (UPR) pathways. The UPR strategy is to enhance protein folding, increase the ER degradation pathway of misfolded proteins, and allow the exit from the ER of only correctly folded proteins. The latter is controlled by the multimeric complex COPII, which also provides some of the components for ER-phagy the only route for the disposal of protein aggregates. In this overview, we wish to contribute to the introduction of new perspectives in the study of the mechanisms underlying the control of proteostasis within the secretory pathway.

Automated summary

The endoplasmic reticulum (ER) is essential for maintaining proteostasis in the secretory pathway through controlling protein folding. The unfolded protein response (UPR) pathways regulate the quality control of protein folding, and the multimeric complex COPII controls the exit of correctly folded proteins from the ER.