Abstract

A large fraction of the proteome is synthesized and folded in the endoplasmic reticulum (ER), a multifunctional compartment also playing pivotal roles in Ca2+ storage, redox homeostasis and signalling. From the ER, secretory proteins begin their journey towards their final destinations, the organelles of the exocytic and endocytic compartments, the plasma membrane or the extracellular space. Fidelity of protein-based intracellular communication is guaranteed by quality control (QC) mechanisms located at the ER – Golgi interface, which restrict forward transport to native proteins. QC is used also to time or shape the secretome. Furthermore, plasma cells and other professional secretory cells face the problem of producing proteins in high quantities. Our recent work on IgM biogenesis sheds light on how cells couple fidelity and efficiency of secretion and identifies ERp44 as a key integrator of protein transport, and Ca2+/redox homeostasis in the early secretory pathway