RIC1-RGP1 exchanges GTP for GDP on RAB6

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).<br><br>

RIC1:RGP1复合体作为RAB6的主要Golgi内运输RAB，在COPI非依赖性逆行运输中亦扮演重要角色。RAB6亦参与高尔基体向内质网的逆行运输。非活性RAB6:GDP通过与RIC1:RGP1相互作用而被招募至转高尔基网络（TGN），随后被RIC1:RGP1 GEF活性所激活（Pusapati等，2012；Siniossoglou等，2001；Siniossoglou等，2000；详见Ishida等，2016年综述）。RIC1:RGP1与RAB6:GDP的相互作用促进GDP的释放，从而允许GTP的结合，并阻止RAB6与GDI和CHM蛋白的相互作用。激活的RAB6在TGN处形成 tethering 复合物，此复合物对于晚期内质体来源的囊泡与囊泡融合是必需的。依赖RAB6的逆行囊泡的典型货物包括驻留的TGN蛋白，如TGOLN2，以及志贺毒素、霍乱毒素和 Ricin毒素，这些毒素利用逆行运输机制‘搭便车’通过分泌系统返回至细胞质中（Siniossoglou等，2001；Liewen等，2005；Perez-Victoria等，2008；Perez-Victoria等，2009；详见Bonaficino和Hierro，2011年综述；Johannes和Popoff，2008；Pfeffer，2011）。