Retrograde transport at the Trans-Golgi-Network

Stable Identifier
Homo sapiens
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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)

Literature References
PubMed ID Title Journal Year
23765164 Retrograde transport of protein toxins through the Golgi apparatus

Sandvig, K, Klokk, TI, Skotland, T, van Deurs, B

Histochem. Cell Biol. 2013
21183348 Transport according to GARP: receiving retrograde cargo at the trans-Golgi network

Hierro, A, Bonifacino, JS

Trends Cell Biol. 2011
9590177 TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking

Pfeffer, SR, Díaz, E

Cell 1998
21421921 Entry at the trans-face of the Golgi

Pfeffer, SR

Cold Spring Harb Perspect Biol 2011
19109890 Tracing the retrograde route in protein trafficking

Popoff, V, Johannes, L

Cell 2008
16936697 Retrograde transport from endosomes to the trans-Golgi network

Rojas, R, Bonifacino, JS

Nat. Rev. Mol. Cell Biol. 2006
19620288 Dual roles of the mammalian GARP complex in tethering and SNARE complex assembly at the trans-golgi network

Pérez-Victoria, FJ, Bonifacino, JS

Mol. Cell. Biol. 2009
25343031 Membrane tethering

Chia, PZ, Gleeson, PA

F1000Prime Rep 2014
18367545 Requirement of the human GARP complex for mannose 6-phosphate-receptor-dependent sorting of cathepsin D to lysosomes

Mardones, GA, Pérez-Victoria, FJ, Bonifacino, JS

Mol. Biol. Cell 2008
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