Sending out molecules from the TGN

Abstract

The sorting of secreted cargo proteins and their export from the trans-Golgi network (TGN) remains an enigma in the field of membrane trafficking; although the sorting mechanisms of many transmembrane proteins have been well described. The sorting of secreted proteins at the TGN is crucial for the release of signaling factors, as well as extracellular matrix proteins. These proteins are required for cell-cell communication and integrity of an organism. Missecretion of these factors can cause diseases such as neurological disorders, autoimmune disease, or cancer. The major open question is how soluble proteins that are not associated with the membrane are packed into TGN derived transport carriers to facilitate their transport to the plasma membrane. Recent investigations have identified novel types of protein and lipid machinery that facilitate the packing of these molecules into a TGN derived vesicle. In addition, novel research has uncovered an exciting link between cargo sorting and export in which TGN structure and dynamics, as well as TGN/endoplasmic reticulum contact sites, play a significant role. Here, we have reviewed the progress made in our understanding of these processes.

Keywords: Cargo sorting; ER-TGN contact sites; Golgi apparatus; Lipid domains; Secreted proteins; TGN.

Figure 1.. Schematic view of protein sorting at the trans-Golgi Network (TGN).

Diagram of the Golgi apparatus and TGN that form membrane contact sites (MCS) with the ER. (A) Schematic model of sorting lysosomal hydrolases into clathrin-coated vesicles the best understood sorting process of soluble proteins at the TGN. (B) Schematic representation of Ca²⁺ and pH dependent “sorting by aggregation” model in neuroendocrine cells. (C) Schematic model of sorting of the PAUF protein into sphingomyelin and cholesterol-rich CARTs. (D) Schematic model depicts the Cab45-dependent client sorting of lysozyme C into sphingomyelin reach vesicles. (E) Schematic model of sorting of Lipoprotein lipase (LPL) protein by Heparan Sulfate modification of Syndecan Iintosphingomyelin reach vesicles. (F) ER/TGN membrane contact site that serve as hotspots for inter-organelle lipid transfer and could play role in Ca²⁺-dependent sorting and signaling between compartments. The Figure was created using Biorender.