Meta-Biol

• Pathways

The trans-Golgi network is the docking site for retrograde cargo from the endolysosomal system and the plasma membrane. Typical cargo includes recycling resident TGN proteins such as TGOLN2 (also known as TGN46), receptors such as the mannose-6-phosphate receptors and toxins like Shiga, cholera and ricin which use the retrograde trafficking machinery to 'hitchhike' back through the secretory system for release into the cytoplasm (reviewed in Johannes and Popoff, 2008; Pfeffer, 2011; Sandvig et al, 2013). These cargo are trafficked from the endocytic system in a clathrin- and AP1-dependent manner that is described in more detail in the "Trans-Golgi network budding pathway" (just not yet). In general, it appears that vesicles are uncoated prior to their tethering and fusion at the TGN. At the TGN, at least 2 distinct tethering pathways exist. A RAB6-dependent pathway contributes to the fusion and docking of vesicles from the early endocytic pathway. These vesicles, which carry cargo such as TGOLN2 and toxins, dock at the TGN through interactions with TGN-localized Golgin tethers and with the multisubunit tethering complexes COG and GARP (reviewed in Bonafacino and Rojas, 2006; Bonafacino and Hierro, 2011; Pfeffer, 2011). In contrast, mannose-6-phosphate receptors appear to traffic from late endosomes to the TGN through a RAB9- and PLIN3-dependent pathway. Vesicles are recruited to the TGN through interaction of RAB9 with the atypical RHO GTPase RHOBTB3, and tethered by virtue of interaction with TGN-localized Golgins and the GARP complex (Perez-Victoria et al, 2008; Perez-Victoria et al, 2009; Diaz et al, 1999; reviewed in Pfeffer, 2011; Chia and Gleeson, 2014)

The secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is made up of distinct organelles, including the endoplasmic reticulum (ER), Golgi complex, plasma membrane, and tubulovesicular transport intermediates. These organelles mediate intracellular membrane transport between themselves and the cell surface. Membrane traffic within this system flows along highly organized directional routes. Secretory cargo is synthesized and assembled in the ER and then transported to the Golgi complex for further processing and maturation. Upon arrival at the trans Golgi network (TGN), the cargo is sorted and packaged into post-Golgi carriers that move through the cytoplasm to fuse with the cell surface. This directional membrane flow is balanced by retrieval pathways that bring membrane and selected proteins back to the compartment of origin.

The transit of proteins and other cargo through the cell requires a cellular transport process in which transported substances are moved in membrane-bounded vesicles. Transported substances are enclosed in the vesicle lumen or located in the vesicle membrane. The transport process begins with the formation of the vesicle itself, often triggered by the interaction of the cargo with the vesicle formation machinery. Vesicular transport pathways can include vesicle formation, coating, budding, uncoating and target membrane fusion depending upon the function of the pathway described. Vesicle-mediated transport occurs from within cell via ER and Golgi transport, as well as functioning in the endocytosis of material taken into the cell via scavenger receptors.