Unraveling the molecular bases of the early protein secretory pathway in humans using biophysical techniques

Abstract

Each and every living cell evolved in a way where an efficient biomolecular secretion system was created in order to attend its basal biological needs and the way they interact with external systems. In this sense, eukaryotic cells enormously differ from prokaryote ones, possessing an extensive biomembrane system in their intracellular part, where different compartments with specific functions are present and require constant exchanges of molecules with each other. Proteins whose final destination is either the extracellular medium or the plasma membrane are initially synthesized within the endoplasmic reticulum (ER) and then addressed to the Golgi complex, where they are packaged and transported to their final destination. Although it has been a subject of intense studies since its discovery, this (classical) pathway of secretion still has several points that need elucidation, especially those related to how proteins are selected in the ER, transported to the Golgi and to how the latter organelle efficiently captures and retains a transport cargo. A family of membrane proteins known as p24 is suggested as the key factor in the process of capturing non-ER proteins and their targeting to the Golgi, as well as an involvement in the Golgi retention process, where it would act together with another protein known as Golgi Reassembly and Stacking Protein (GRASP). With this proposal, we intend to provide key information on the mechanism of action of p24 in humans, its retention process in the Golgi and their involvement in membrane expression of protein receptors with roles in pro-inflammatory responses. (AU)