Meta-Biol

• Pathways

RAB1 is involved in COPII-mediated anterograde traffic from the endoplasmic reticulum to the ERGIC (ER-Golgi intermediate compartment) and in early steps of the macroautophagy pathway (reviewed in Szul and Sztul, 2011; Sandoval and Simmen, 2012; Lord et al, 2013; Yang et al, 2016; Lamb et al, 2016; Kim et al, 2016; Ao et al, 2014). RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III, respectively (reviewed in Brunet and Sacher, 2014; Kim et al, 2016). Note that the separate existence of a TRAPPCI complex is not clearly established in human cells (Barrowman et al, 2010; Bassik et al, 2013; reviewed in Brunet and Sacher, 2014; Kim et al, 2016). TRAPPCII is recruited to ER-derived vesicles by virtue of an interaction between the TRAPPCII component TRAPPC3 and the COPII coat protein SEC23 (Wang et al, 2000; Cai et al, 2007; Cai et al, 2008; Yamasaki et al, 2009; Lord et al, 2011; reviewed in Brunet and Sacher, 2014; Ishida et al, 2016). Interaction of TRAAPPCII with RAB1:GDP promotes release of GDP, allowing GTP to bind, and precludes the interaction of RAB1 with GDI and CHM proteins. Protein protein interactions involving activated RAB1:GTP help dock the ER-derived vesicle on the cis-Golgi membrane (reviewed in Lord et al, 2013). In the macroautophagy pathway, RAB1 and the TRAPPCIII complex play a role in the formation of the pre-autophagosomal structure (PAS) and contribute to the localization of ATG9, a key nucleator of autophagosome formation (Lynch-Day et al, 2010; Winslow et al, 2010; Zoppino et al, 2010; Mochizuki et al, 2013; Lamb et al, 2016; reviewed in Kim et al, 2016).