Rab6-mediated retrograde trafficking from the Golgi: the trouble with tubules

Figures & data

Table 1. List of Rab6 effectors and interacting proteins.

Protein	Comment	Proposed role in Golgi-to-ER transport	Reference
Bicaudal D1 (BicD1)	Interacts with C-terminal of GTP-locked Rab6A; thought to play a role in Rab6-dependent endocytic transport but its role in Golgi-ER transport, if any, is less well defined	Motility^?	[61,64]
Bicaudal D2 (BicD2)	Interacts with C-terminal of GTP-locked Rab6A; thought to play roles in both the motility of Rab6-dependent Golgi-ER carriers and the fusion of these carriers with the ER membrane	Motility; fusion	[61,64]
Dynein light chain roadblock-type 1 (DYNLRB1)	Identified as an effector of Rab6A, Rab6A’ and Rab6B through co-immunoprecipitation, yeast two-hybrid and pull down studies	Motility	[65]
GAPCenA/RabGAP1	Rab6 GAP; localizes to centrosomes and understood to be involved in microtubule nucleation	None	[66]
GCC185	Contains a Rab-binding domain upstream of its C-terminal GRIP domain	None	[67]
Giantin	N-terminal of Giantin interacts directly with the N-terminal of GTP-locked Rab6A; interaction between Rab6 and Giantin decreases upon pharmacologically induced Golgi destabilization	Biogenesis^?	[47,68]
Golgin-97	Contains Rab6-interacting domain at C-terminal	None	[69]
Golgin-245	Contains Rab6-interacting domain at C-terminal	None	[69]
Golgin, Rab6 interacting (GORAB; aka SCYL1BP1)	Identified as an interactor with both Rab6A and Rab6B in yeast two-hybrid studies; later identified as COPI scaffolding factor	None	[70,71]
KIF1C	Binds to Rab6A at both the C-terminus and the motor domain; binding of Rab6A at the motor domain inhibits the interaction of KIF1C with microtubules	None	[72]
KIF5B	Shown to facilitate Rab6-dependent exocytosis, not yet been shown to be involved in Rab6-dependent Golgi-ER transport	Motility*	[51]
KIF20A	Binds to Rab6 via the C-terminus, plays a role in the fission of Rab6-dependent anterograde carriers	Motility^?*; fission*	[52]
LIS1	GTP-locked Rab6A releases LIS1 from dynein idling complex – no direct binding reported	Motility^?	[73]
Mint3/APBA3	The phosphotyrosine-binding (PTB) domain interacts with GTP-locked Rab6A; confirmed through yeast two-hybrid studies and FRET	None	[74,75]
Non-muscle myosin 2A (NM2A)	Coiled-coil heavy chain region shown to interact with GTP-locked Rab6A and Rab6A’ through yeast-two-hybrid studies; important for biogenesis of Rab6-dependent Golgi-ER carriers and fission of Rab6-dependent anterograde carriers	Biogenesis; fission*	[42]
Non-muscle myosin 2B (NM2B)	Coiled-coil heavy chain region interacts with GTP-locked Rab6A and Rab6A’, identified through yeast two-hybrid studies	None	[42]
OCRL1	Identified as a Rab6 interactor through yeast two-hybrid studies; contains a Rab-binding domain also capable of binding to Rab1B, Rab5A and Rab8A in addition to Rab6A	None	[76]
p150^glued	Identified as an interactor of Rab6 through yeast-two-hybrid studies; capable of interacting with wild-type Rab6 but preferentially interacts with GTP-locked Rab6	Motility^?	[64]
Rab6IP1/ DENND5	Identified as a Rab6 effector through yeast-two-hybrid studies and pull-down experiments; binds to Rab6 through a central RUN domain	None	[77,78]
Rab6IP2/ELKS	Contains a Rab6-binding domain at the C-terminus; in-vitro studies show preferential binding to Rab6B and Rab6A’ over Rab6A; potentially involved in Rab6-dependent endosome-Golgi transport	None	[79]
TGN38	Cytoplasmic, carboxy-terminal domain binds to a complex of Rab6 with p62; is thought to play a role in the budding of exocytic vesicles but has not been studied in the context of Rab6-dependent Golgi-ER traffic	None	[80]
TMF/ARA160	Contains a coiled-coil motif that is capable of binding to Rab6A, Rab6A’ and Rab6B; thought to play an as yet undefined role in Rab6-dependent Golgi-ER carrier biogenesis	Biogenesis	[46]

*Identified as playing a role in Rab6-dependent anterograde transport.

^?Possible role in Rab6-dependent Golgi-to-ER transport, yet to be experimentally validated.

Figure 1. De-scaffolding of the Golgi apparatus. Schematic diagram outlining the likely order of ‘de-scaffolding’ of the Golgi membrane in order to generate a Rab6-positive tubular carrier.

Figure 2. An overview of Rab6-dependent Golgi-to-ER transport. Schematic outlining our current understanding of molecules involved in the different steps of Rab6-dependent Golgi-to-ER transport (a: biogenesis, b: motility and elongation, c: tubule fission, d: tubule fusion at the ER). Proteins speculated but not explicitly confirmed to play a role in this pathway are indicated with a ‘?’, and proteins confirmed to play a role in mediating anterograde Rab6-dependent transport, but have not been investigated in the context of retrograde transport, are marked with an asterisk.

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