Chaperones in the Endoplasmic Reticulum (ER): Function and Interaction Network

The directional entry, oxidative folding, and quality control of proteins that enter the secretory pathway is mediated by chaperones and foldases in and adjacent to the endoplasmic reticulum (ER). Properly folded and assembled proteins continue along the secretory pathway while proteins that ultimately fail quality control are targeted to the proteasome by removal from the ER in a process called ER-associated degradation (ERAD). The protein folding machineries in the ER interact with each other to form functional complexes. Studies have revealed that abundant chaperones and foldases serve multiple functions in the ER through membership in diverse complexes that can target their activities to substrates at different stages of maturation. These findings are providing insight into how ER complexes combine various functions together to engage substrates and determine their fates.