RIC1-RGP1 exchanges GTP for GDP on RAB6

Stable Identifier
Reaction [transition]
Homo sapiens
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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

Mardones, GA, Pérez-Victoria, FJ, 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

Pelham, HR, Siniossoglou, S

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

Pfeffer, SR, Luchetti, G, Pusapati, GV

J. Biol. Chem. 2012
19109890 Tracing the retrograde route in protein trafficking

Popoff, V, Johannes, L

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

Pelham, HR, Siniossoglou, S, Peak-Chew, SY

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

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
27246931 Multiple Types of Guanine Nucleotide Exchange Factors (GEFs) for Rab Small GTPases

Oguchi, ME, Fukuda, M, Ishida, M

Cell Struct. Funct. 2016
Catalyst Activity

guanyl-nucleotide exchange factor activity of RIC1:RGP1 [cytosol]

Orthologous Events
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