Reactome | RIC1-RGP1 exchanges GTP for GDP on RAB6

RIC1-RGP1 exchanges GTP for GDP on RAB6

Stable Identifier

R-HSA-8876193

Type

Reaction [transition]

Species

Homo sapiens

Compartment

trans-Golgi network membrane, cytosol

ReviewStatus

5/5

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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).

Literature References

PubMed ID	Title	Journal	Year
18367545	Requirement of the human GARP complex for mannose 6-phosphate-receptor-dependent sorting of cathepsin D to lysosomes Pérez-Victoria, FJ, Mardones, GA, Bonifacino, JS	Mol. Biol. Cell	2008
11689439	An effector of Ypt6p binds the SNARE Tlg1p and mediates selective fusion of vesicles with late Golgi membranes Siniossoglou, S, Pelham, HR	EMBO J.	2001
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 Pusapati, GV, Luchetti, G, Pfeffer, SR	J. Biol. Chem.	2012
19109890	Tracing the retrograde route in protein trafficking Johannes, L, Popoff, V	Cell	2008
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
10990452	Ric1p and Rgp1p form a complex that catalyses nucleotide exchange on Ypt6p Siniossoglou, S, Peak-Chew, SY, Pelham, HR	EMBO J.	2000
25341920	Rab proteins and the compartmentalization of the endosomal system Wandinger-Ness, A, Zerial, M	Cold Spring Harb Perspect Biol	2014
21421921	Entry at the trans-face of the Golgi Pfeffer, SR	Cold Spring Harb Perspect Biol	2011
21183348	Transport according to GARP: receiving retrograde cargo at the trans-Golgi network Bonifacino, JS, Hierro, A	Trends Cell Biol.	2011
15878329	Characterization of the human GARP (Golgi associated retrograde protein) complex Liewen, H, Meinhold-Heerlein, I, Oliveira, V, Schwarzenbacher, R, Luo, G, Wadle, A, Jung, M, Pfreundschuh, M, Stenner-Liewen, F	Exp. Cell Res.	2005
27246931	Multiple Types of Guanine Nucleotide Exchange Factors (GEFs) for Rab Small GTPases Ishida, M, Oguchi, ME, Fukuda, M	Cell Struct. Funct.	2016