Meta-Biol

• Pathways

The RIC1:RGP1 complex is a GEF for RAB6, the primary RAB in intra-Golgi trafficking. RAB6 also has roles in COPI-independent retrograde traffic from the Golgi to the ER. Inactive RAB6:GDP is recruited to the trans-Golgi network (TGN) through interaction with RIC1:RGP1, and is subsequently activated by the RIC1:RGP1 GEF activity (Pusapati et al, 2012; Siniossoglou et al 2001; Siniossoglou et al, 2000; reviewed in Ishida et al, 2016). Interaction of RIC1:RGP1 with RAB6:GDP promotes release of GDP, allowing GTP to bind, and precludes the interaction of RAB6 with GDI and CHM proteins. Activated RAB6 nucleates a tethering complex at the TGN that is required for fusion of endosome-derived vesicles arriving at the late Golgi. Typical cargo of the RAB6-dependent retrograde vesicles include resident TGN proteins such as TGOLN2 as well as Shiga, cholera and ricin toxins which use the retrograde trafficking machinery to 'hitchhike' back through the secretory system for release into the cytoplasm (Siniossoglou et al, 2001; Liewen et al, 2005; Perez-Victoria et al, 2008; Perez-Victoria et al, 2009; reviewed in Bonaficino and Hierro, 2011; Johannes and Popoff, 2008; Pfeffer, 2011).