RAB6:GTP binds the GARP and COG complexes, t-SNAREs and endosome-derived vesicles

Stable Identifier
Reaction [binding]
Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
21807881 The COG complex interacts directly with Syntaxin 6 and positively regulates endosome-to-TGN retrograde transport

Hong, W, Lev, S, Laufman, O

J. Cell Biol. 2011
18195106 A syntaxin 10-SNARE complex distinguishes two distinct transport routes from endosomes to the trans-Golgi in human cells

Pfeffer, SR, Espinosa, E, Ganley, IG

J. Cell Biol. 2008
18946081 Multiple Rab GTPase binding sites in GCC185 suggest a model for vesicle tethering at the trans-Golgi

Brown, FC, Hayes, GL, Nottingham, RM, Barr, FA, Haas, AK, Pfeffer, SR

Mol. Biol. Cell 2009
11839770 Early/recycling endosomes-to-TGN transport involves two SNARE complexes and a Rab6 isoform

Yue, X, Galli, T, Hong, W, Saint-Pol, A, Johannes, L, Tenza, D, Tang, BL, Goud, B, Antony, C, Mallard, F

J. Cell Biol. 2002
15654769 The trans-Golgi network GRIP-domain proteins form alpha-helical homodimers

Luke, MR, Perugini, MA, Houghton, F, Gleeson, PA

Biochem. J. 2005
10637310 Vps52p, Vps53p, and Vps54p form a novel multisubunit complex required for protein sorting at the yeast late Golgi

Conibear, E, Stevens, TH

Mol. Biol. Cell 2000
20685960 Ang2/fat-free is a conserved subunit of the Golgi-associated retrograde protein complex

Delevoye, C, Raposo, G, Mardones, GA, Magadán, JG, Romao, M, Pérez-Victoria, FJ, Bonifacino, JS, Schindler, C

Mol. Biol. Cell 2010
21421921 Entry at the trans-face of the Golgi

Pfeffer, SR

Cold Spring Harb Perspect Biol 2011
15269279 Autoantigen Golgin-97, an effector of Arl1 GTPase, participates in traffic from the endosome to the trans-golgi network

Hong, W, Tai, G, Lu, L

Mol. Biol. Cell 2004
21436057 The golgin coiled-coil proteins of the Golgi apparatus

Munro, S

Cold Spring Harb Perspect Biol 2011
18256213 Large scale screening for novel rab effectors reveals unexpected broad Rab binding specificity

Fukuda, M, Itoh, T, Kanno, E, Ishibashi, K

Mol. Cell Proteomics 2008
16885419 A functional role for the GCC185 golgin in mannose 6-phosphate receptor recycling

Reddy, JV, Burguete, AS, Nottingham, RM, Sridevi, K, Pfeffer, SR, Ganley, IG

Mol. Biol. Cell 2006
17562788 Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways

Spooner, RA, Barr, FA, Lord, JM, Haas, AK, Yoshimura, S, Fuchs, E

J. Cell Biol. 2007
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
23091056 Ric1-Rgp1 complex is a guanine nucleotide exchange factor for the late Golgi Rab6A GTPase and an effector of the medial Golgi Rab33B GTPase

Pfeffer, SR, Luchetti, G, Pusapati, GV

J. Biol. Chem. 2012
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
22581368 Are Rab proteins the link between Golgi organization and membrane trafficking?

Storrie, B, Liu, S

Cell. Mol. Life Sci. 2012
17488291 The trans-Golgi network golgin, GCC185, is required for endosome-to-Golgi transport and maintenance of Golgi structure

Derby, MC, Goud, B, Brown, D, Lieu, ZZ, Stow, JL, Gleeson, PA

Traffic 2007
21183348 Transport according to GARP: receiving retrograde cargo at the trans-Golgi network

Hierro, A, Bonifacino, JS

Trends Cell Biol. 2011
15878329 Characterization of the human GARP (Golgi associated retrograde protein) complex

Schwarzenbacher, R, Jung, M, Liewen, H, Pfreundschuh, M, Meinhold-Heerlein, I, Oliveira, V, Luo, G, Wadle, A, Stenner-Liewen, F

Exp. Cell Res. 2005
15870108 tGolgin-1 (p230, golgin-245) modulates Shiga-toxin transport to the Golgi and Golgi motility towards the microtubule-organizing centre

Poynton, C, Whiteman, EL, Setty, SR, Saint-Pol, A, Johannes, L, Holzbaur, EL, McCaffery, JM, Marks, MS, Burd, CG, Koval, M, Yoshino, A

J. Cell. Sci. 2005
12377769 Vps51p links the VFT complex to the SNARE Tlg1p

Pelham, HR, Siniossoglou, S

J. Biol. Chem. 2002
17684057 Analysis of GTPase-activating proteins: Rab1 and Rab43 are key Rabs required to maintain a functional Golgi complex in human cells

Barr, FA, Haas, AK, Stephens, DJ, Yoshimura, S, Fuchs, E, Preisinger, C

J. Cell. Sci. 2007
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