Identifier: R-HSA-6811431
Compartment:
trans-Golgi network membrane
Active RAB6 contributes to the recruitment of the Golgi-associated retrograde protein (GARP) tethering complex to the TGN, where it aids in the capture of retrograde vesicles from the early endosome (Liewen et al, 2005; reviewed in Bonifacino and Hierro, 2011). Typical cargo of these vesicles includes resident TGN proteins such as TGOLN2 (also known as TGN46) and internalized Shiga toxin subunit B (STx-B) and cholera toxin (Perez-Victoria et al, 2008; Ganley et al 2008; Pusapati et al, 2012; reviewed in Pfeffer, 2011; Liu and Storrie, 2012). Two studies have identifed RAB43 and its associated GAP USP6NL as being required for the retrograde traffic of Shiga toxin, however the details of this remain to be worked out (Haas et al, 2007; Fuchs et al, 2007).
The human GARP complex consists of VPS54, VPS53, VPS52 and VPS51 and has been shown to interact with GTP-bound RAB6, with the TGN SNAREs STX10 and STX16 and with a vesicle fraction containing the v-SNARE VAMP4 (Connibear et al, 2000; Liewen et al, 2005; Perez-Victoria et al, 2009; Perez-Victoria et al, 2010; Siniossoglou and Pelham, 2002; reviewed in Bonafacino and Hierro, 2011).
Like the GARP complex, the conserved oligomeric Golgi (COG) complex has also been implicated in retrograde traffic of TGOLN2 and STx-B in a STX6:STX16:VTI1A and VAMP4-dependent manner, and COG has been shown to interact directly with RAB6 (Mallard et al, 2002; Fukuda et al, 2008; Laufman et al, 2011; reviewed in Pfeffer, 2011). Despite the representation in this reaction, however, there is not yet evidence that the GARP and the COG complexes act together to facilitate the capture of a single early endosome-derived vesicle.
In addition to the multisubunit tethering complexes COG and GARP, the long coiled-coil TGN-associated Golgins also contribute to tethering of vesicles derived from the early endosome (Luke et al, 2005; Derby et al, 2007; Reddy et al, 2006; Lu et al, 2004; Yoshino et al, 2005; Hayes et al, 2009; reviewed in Munro, 2011).