Retrograde transport at the Trans-Golgi-Network

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)

Summary from Reactome (R-HSA-6811440), read 2026-09-23.