Endoplasmic reticulum and Golgi stress signaling-mediated regulation of protein secretion

The eukaryotic secretory pathway (SP) is essential to ensure cellular functions and multicellular communication. The early SP is constituted mostly of the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment (ERGIC), and the Golgi apparatus. These intracellular organelles achieve proper folding and modification of newly synthesized transmembrane and secretory proteins, en route to their final destination, e.g., plasma membrane, endosomes, lysosomes, and the extracellular space. They also integrate quality control systems to ensure export of productively folded proteins and to trigger dysfunctional proteins to degradation. The ER as the first SP compartment is subjected to a precise control of its own homeostasis through signaling of the unfolded protein response. In this review, we provide an overview of the early SP and its regulatory mechanisms, focusing on the ER and Golgi stress-dependent signaling. We contextualize this information within physiological and pathological processes, and discuss how ER and Golgi stress responses might coordinate their regulatory effects across the entire SP.