The Unfolded Protein Response in Secretory Cell Function

The endoplasmic reticulum (ER) controls many important aspects of cellular function, including processing of secreted and membrane proteins, synthesis of membranes, and calcium storage. Maintenance of ER function is controlled through a network of signaling pathways collectively known as the unfolded protein response (UPR). The UPR balances the load of incoming proteins with the folding capacity of the ER and allows cells to adapt to situations that disrupt this balance. This disruption is referred to as ER stress. Although ER stress often arises in pathological situations, the UPR plays a central role in the normal development and function of cells specializing in secretion. Many aspects of this response are conserved broadly across eukaryotes; most organisms use some subset of a group of ER transmembrane proteins to signal to the nucleus and induce a broad transcriptional upregulation of genes involved in ER function. However, new developments in metazoans, plants, and fungi illustrate interesting variations on this theme. Here, we summarize mechanisms for detecting and counteracting ER stress, the role of the UPR in normal secretory cell function, and how these pathways vary across organisms and among different tissues and cell types.