Affinage

RAB6A

Ras-related protein Rab-6A · UniProt P20340

Length
208 aa
Mass
23.6 kDa
Annotated
2026-04-28
100 papers in source corpus 45 papers cited in narrative 45 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB6A is a Golgi-associated small GTPase essential for multiple membrane trafficking pathways, including COPI-independent retrograde transport from Golgi to ER, retrograde endosome-to-TGN transport (primarily via the Rab6A' splice isoform), and anterograde secretory vesicle delivery to the plasma membrane at focal adhesion-associated hotspots (PMID:7798313, PMID:10562278, PMID:31142554). In its GTP-bound form, RAB6A recruits a diverse array of effectors—kinesin motors (KIF20A, kinesin-1, KIF1C), the dynein/dynactin complex (via DYNLRB1, p150Glued, and BicaudalD2), golgins (TMF, GORAB, golgin-245/97, COH1), and the cortical docking factor ELKS—to coordinate microtubule-dependent vesicle motility, Golgi cisternal organization, and cargo-specific exocytosis including TNF secretion in macrophages, melanosomal cargo delivery, TrkB receptor axonal transport, and LAT recycling for TCR signaling (PMID:9438855, PMID:12401177, PMID:17681140, PMID:28607494, PMID:29440364, PMID:33571451). Its GTPase cycle is controlled by the Ric1/Rgp1 GEF complex and the GAP GAPCenA, while membrane targeting depends on C-terminal geranylgeranylation and GDI-mediated cytosol–membrane cycling; the Rab6A' isoform additionally regulates mitotic progression through dynein/dynactin dynamics at kinetochores (PMID:23091056, PMID:10202141, PMID:8264642, PMID:16395330). Loss-of-function mutations in the RAB6 effector GORAB (SCYL1BP1) cause gerodermia osteodysplastica, a connective tissue disorder linked to disrupted RAB6-dependent Golgi function (PMID:18997784, PMID:26000619).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1994 High

    The first functional role for Rab6 was established as a regulator of intra-Golgi transport between cis/medial and trans compartments, resolving which trafficking step this GTPase controls.

    Evidence Overexpression of GTP-locked (Q72L) and GDP-locked (T27N) Rab6 mutants in HeLa and L cells with SEAP and HA transport assays

    PMID:7798313

    Open questions at the time
    • Directionality (anterograde vs retrograde) not yet resolved
    • Effector proteins unknown
    • Whether Rab6 acts directly or indirectly on membrane fusion unresolved
  2. 1994 High

    The membrane targeting mechanism of Rab6 was defined: geranylgeranylation at the C-terminal CXC motif and N-terminal effector domain sequences are required for Golgi localization and GDI-mediated membrane extraction, establishing the lipid modification and structural determinants of Rab6 cycling.

    Evidence Chimeric Ras-Rab proteins, C-terminal lipid modification mutants, in vitro GDI extraction assays, and yeast complementation

    PMID:8175798 PMID:8264642

    Open questions at the time
    • Structural basis for GDI-Rab6 interaction not determined
    • How effector domain contributes to both GDI binding and Golgi targeting not mechanistically separated
  3. 1997 High

    Rab6 was shown to drive a microtubule-dependent Golgi-to-ER retrograde transport pathway distinct from COPI-mediated transport, fundamentally redefining Rab6 as a retrograde trafficking regulator rather than solely an intra-Golgi factor.

    Evidence GTP-locked Rab6 overexpression redistributed trans-Golgi markers to ER in HeLa cells; microtubule depolymerization blocked the effect; live imaging showed COPI exclusion from Rab6 carriers

    PMID:10562278 PMID:9050864

    Open questions at the time
    • Motor proteins responsible for microtubule-dependent movement not yet identified
    • Cargo selectivity of the COPI-independent pathway undefined
  4. 1998 High

    Identification of Rabkinesin-6 (KIF20A) as the first Rab6 effector provided a direct molecular link between Rab6 and motor-dependent transport, answering how Rab6 drives microtubule-based vesicle movement.

    Evidence Two-hybrid screen, co-immunoprecipitation, and dominant-negative inhibition of Rab6-dependent transport by KIF20A C-terminus

    PMID:9438855

    Open questions at the time
    • Whether KIF20A is the motor for Golgi-to-ER transport or has other roles (e.g., mitosis) not separated
    • Other effectors likely exist
  5. 1999 High

    Discovery of GAPCenA as a Rab6-specific GAP and golgin-245/97 as Rab6-binding tethering factors established the regulatory and structural framework for Rab6-dependent Golgi trafficking.

    Evidence In vitro GAP assays showing specificity for Rab6; protein blot binding and mutagenesis linking golgin Golgi targeting to Rab6 interaction

    PMID:10202141 PMID:10209123

    Open questions at the time
    • GEF for Rab6 not yet identified
    • Functional consequence of golgin-Rab6 binding on vesicle tethering not directly tested
  6. 2000 High

    Cloning of the Rab6A' splice isoform revealed that a single amino acid difference (position 87) uncouples Rab6A from Rab6A' effector binding and Golgi-to-ER transport function, establishing isoform-specific roles from a single gene.

    Evidence Molecular cloning showing 3-amino-acid difference; yeast two-hybrid demonstrating loss of Rabkinesin-6 binding by Rab6A'; overexpression failing to redistribute Golgi markers to ER

    PMID:11071909

    Open questions at the time
    • Rab6A'-specific effectors not yet identified
    • Whether Rab6A' has distinct trafficking functions unknown at this point
  7. 2002 High

    Rab6A' was assigned to a distinct retrograde pathway—early/recycling endosome-to-TGN transport—working with specific SNARE complexes, while Rab6A was confirmed in Golgi-to-ER transport; dynactin was identified as a Rab6-specific Golgi membrane recruitment target, resolving how Rab6 engages the minus-end-directed motor machinery.

    Evidence Permeabilized cell transport assay with SNARE identification for Rab6A'; pulldown and membrane recruitment assays showing Rab6-specific dynactin binding

    PMID:11839770 PMID:12401177

    Open questions at the time
    • How Rab6 coordinates dynactin versus golgin tethering not resolved
    • Whether dynactin recruitment is sufficient for retrograde transport or requires additional factors
  8. 2006 High

    Rab6A' was found to have a cell-cycle-specific role: its depletion arrests cells in metaphase by activating the Mad2 spindle checkpoint, with p150Glued retained at kinetochores, revealing an unexpected mitotic function for a Golgi Rab.

    Evidence Isoform-specific siRNA; time-lapse imaging of mitotic arrest; immunofluorescence for checkpoint markers; epistasis with GAPCenA

    PMID:16395330 PMID:16536738

    Open questions at the time
    • How Rab6A' regulates dynein/dynactin at kinetochores mechanistically unclear
    • Whether mitotic and trafficking functions are fully separable at the molecular level
  9. 2007 High

    Rab6 was shown to control anterograde exocytotic transport by marking secretory vesicles that move processively to the cell periphery via kinesin-1 and dock at ELKS-enriched plasma membrane sites, establishing Rab6 as a bidirectional trafficking coordinator.

    Evidence Live-cell imaging; siRNA; co-immunoprecipitation identifying ELKS as Rab6 effector; vesicle motility assays

    PMID:17681140

    Open questions at the time
    • How Rab6 switches between retrograde and anterograde effector engagement unknown
    • Cargo selectivity of anterograde Rab6 carriers undefined
  10. 2008 High

    Biophysical characterization of Rab6a-effector interactions (BicaudalD2, p150Glued, PIST) and identification of DYNLRB1 as a direct dynein-Rab6 link established the quantitative and structural basis for effector recognition and motor complex assembly.

    Evidence ITC, fluorescence kinetics, and GTPase assays for effector binding; yeast two-hybrid and co-IP for DYNLRB1 across all isoforms

    PMID:18044744 PMID:19019823

    Open questions at the time
    • How multiple effectors compete or cooperate on the same Rab6-positive membrane not resolved
    • Crystal structure with dynein components lacking
  11. 2009 High

    The crystal structure of Rab6a-GTP bound to the RUN domain of Rab6IP1 revealed how conformational flexibility in Rab6's hydrophobic triad enables recognition of structurally distinct effectors, providing a structural explanation for effector diversity.

    Evidence X-ray crystallography at 3.2 Å resolution; comparison with Rab6-GCC185 complex structure

    PMID:19141279

    Open questions at the time
    • Structures with motor effectors (kinesins, dynactin) not available
    • How effector switching is regulated in vivo remains unknown
  12. 2012 High

    Identification of Ric1/Rgp1 as the Rab6A GEF, activated downstream of Rab33B, completed the core GTPase cycle machinery and revealed a Rab cascade linking medial and trans-Golgi compartments.

    Evidence In vitro nucleotide exchange assay; co-IP of Rab33B-GTP with Ric1; siRNA causing loss of Rab6 and blocked mannose-6-phosphate receptor transport

    PMID:23091056

    Open questions at the time
    • Structural basis for Ric1/Rgp1 catalytic mechanism unknown
    • Whether other GEFs exist for Rab6 in specific cell types not addressed
  13. 2015 High

    RAB6A knockout mice established RAB6A as an essential gene required for embryonic development; MEF analysis confirmed roles in Golgi morphology, secretion, and toxin sensitivity, validating decades of overexpression and RNAi studies.

    Evidence Conditional knockout mouse; 4-OHT-induced Cre deletion in MEFs; multiple phenotypic readouts (Golgi morphology, VSV-G secretion, ricin resistance)

    PMID:26304202

    Open questions at the time
    • Tissue-specific requirements not fully explored
    • Relative contributions of Rab6A vs Rab6A' in vivo not genetically separated in this study
  14. 2017 High

    Cell-type-specific functions of RAB6 were demonstrated in melanocytes, where RAB6/ELKS-dependent carriers deliver cargo directly to melanosomes rather than the plasma membrane, and in T cells, where Rab6-dependent retrograde transport of LAT controls TCR signaling and immune synapse formation.

    Evidence Live imaging and Rab6 KO mice showing pigmentation defects; siRNA and Rab6 KO T cells with impaired TCR stimulation and LAT mislocalization

    PMID:28607494 PMID:29440364

    Open questions at the time
    • How ELKS discriminates melanosome versus plasma membrane targeting unknown
    • Whether other immune signaling adaptors use Rab6 retrograde transport not tested
  15. 2019 High

    A comprehensive secretion study established that RAB6-positive carriers are the dominant class of post-Golgi secretory carriers for diverse cargos, and that exocytosis occurs at spatially restricted hotspots near focal adhesions.

    Evidence RUSH synchronized secretion assay tracking multiple cargo types; RAB6 siRNA; live-cell imaging with spatial analysis

    PMID:31142554

    Open questions at the time
    • Molecular mechanism linking focal adhesions to exocytic hotspots not defined
    • Whether all cell types use focal adhesion-proximal secretion sites unknown
  16. 2022 High

    In developing neocortex, RAB6A/A' and RAB6B double knockout demonstrated that RAB6-dynein-LIS1 complexes transport vesicles to the apical surface of radial glia, and this transport is essential for CRB3 polarization and proper cortical development.

    Evidence In situ live imaging in developing neocortex; conditional double KO; epistasis with LIS1 KO

    PMID:35979738

    Open questions at the time
    • Whether RAB6 directly activates dynein via LIS1 or acts in parallel unknown
    • Cargo selectivity of apical-directed RAB6 carriers in neural progenitors not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions remain: how Rab6 switches between retrograde and anterograde effectors on the same membrane, the structural basis for effector competition and motor coordination, whether tissue-specific GEFs or GAPs diversify Rab6 function, and the precise mechanism coupling Rab6 exocytosis to focal adhesion hotspots.
  • No structural model for Rab6 engaged with motor complexes (dynein or kinesin-1) on membranes
  • Mechanism of effector switching or handoff between retrograde and anterograde motors unresolved
  • No systematic identification of tissue-specific Rab6 regulators

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 5 GO:0098772 molecular function regulator activity 4
Localization
GO:0005794 Golgi apparatus 6 GO:0031410 cytoplasmic vesicle 4 GO:0005829 cytosol 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 7 R-HSA-9609507 Protein localization 5 R-HSA-1640170 Cell Cycle 3 R-HSA-1266738 Developmental Biology 2 R-HSA-168256 Immune System 1
Partners
BICD2DCTN1DYNLRB1ELKSGORABKIF1CKIF20ATMF1

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Rab6 controls intra-Golgi transport, specifically between cis/medial and late (trans) Golgi compartments; overexpression of GTP-bound (Q72L) or wild-type Rab6 blocks transport between these compartments without affecting ER-to-cis/medial Golgi or TGN-to-plasma membrane transport. Transient overexpression of wild-type, GTP-bound (Q72L) and GDP-bound (T27N) mutants in HeLa and L cells; intracellular transport assays with SEAP and influenza HA The Journal of cell biology High 7798313
1994 Golgi apparatus localization of Rab6 requires geranylgeranylation at its CXC C-terminal motif and sequences within the N-terminal 71 amino acids (including the effector domain); farnesylation alone cannot substitute for geranylgeranylation in Golgi targeting. Chimeric Ras-Rab proteins, C-terminal lipid modification mutants, immunofluorescence, yeast complementation assay Molecular and cellular biology High 8264642
1994 Geranylgeranylation on CXC or CC motifs is required for efficient membrane extraction of Rab6 by RabGDI; the effector domain, loop3/beta3, and hypervariable region of Rab6 are all required for RabGDI binding, while loop3/beta3 and hypervariable region (but not the effector domain) are required for RabGGTase processing. In vitro RabGDI membrane extraction assay with Rab6 mutants carrying various C-terminal lipid modifications; mutagenesis The Journal of biological chemistry High 8175798
1995 GDI beta interacts with wild-type Rab6 and Rab5 but not with a GTP-bound Rab6 mutant, and recombinant GDI beta can remove Rab6 (and other Rabs including Rab1, Rab2, Rab4) from membranes. Yeast two-hybrid screen; recombinant GDI beta membrane extraction assay The Journal of biological chemistry High 7782346
1996 Rab6 antibodies and a trans-dominant Rab6 mutant (N126I) inhibit transport between cis and medial Golgi cisternae and inhibit fusion of Golgi membranes in a cell-free reconstituted transport system, indicating Rab6 is required for membrane fusion at Golgi cisternal membranes. Reconstituted in vitro Golgi transport assay; inhibition with polyclonal antibodies, Fab fragments, and dominant-negative Rab6 N126I mutant The Journal of biological chemistry High 8663167
1997 GTP-bound Rab6 (Q72L) and wild-type Rab6 overexpression induces microtubule-dependent redistribution of trans-Golgi proteins (beta-1,4-galactosyltransferase) into the ER, phenocopying brefeldin A effects; this retrograde Golgi-to-ER transport requires intact microtubules. Overexpression of wild-type and GTP/GDP mutants of Rab6 in HeLa cells; immunofluorescence and biochemical analyses; microtubule depolymerization experiments Proceedings of the National Academy of Sciences of the United States of America High 9050864
1998 Rab6 binds specifically to the GTP-bound form of Rab6, and this interaction is mediated by the C-terminal domain of Rabkinesin-6 (KIF20A); Rabkinesin-6 localizes to the Golgi apparatus and its overexpression (C-terminal domain) inhibits Rab6-GTP effects on intracellular transport, identifying a kinesin motor as a Rab6 effector. Two-hybrid screen; co-immunoprecipitation; immunofluorescence localization; dominant-negative overexpression transport assay Science High 9438855
1999 Rab6 regulates a COPI-independent Golgi-to-ER retrograde transport pathway; Rab6-positive transport carriers specifically carry retrograde cargo (Shiga toxin B-fragment) and associate with ER; Rab6:GDP (T27N) overexpression inhibits Shiga holotoxin cytotoxicity without blocking STB transport to the Golgi; COPI markers are excluded from Rab6/STB transport carriers. Live fluorescence imaging of FP-Rab6 with secretory pathway markers; COPI antibody microinjection; vaccinia-T7 overexpression of Rab6 T27N; confocal and time-lapse microscopy The Journal of cell biology High 10562278
1999 GAPCenA is a novel GAP specifically active on Rab6 in vitro (and to lesser extent on Rab4 and Rab2); GAPCenA is predominantly cytosolic with a minor pool at the centrosome, forms complexes with gamma-tubulin, and plays a role in microtubule nucleation. In vitro GAP activity assay on recombinant Rab proteins; immunofluorescence; cell fractionation; co-immunoprecipitation with gamma-tubulin The EMBO journal High 10202141
1999 Golgins golgin-230/245/256 and golgin-97 target to the Golgi apparatus through a conserved C-terminal domain containing a critical tyrosine residue that preferentially binds Rab6; mutations abolishing Golgi targeting also abolish Rab6 binding, identifying a Rab6-interacting domain defining a family of Golgi-targeted coiled-coil proteins. Protein blot binding assay; mutagenesis; Golgi targeting assays; sequence analysis Current biology High 10209123
2000 Rab6A and Rab6A' are two distinct isoforms generated by alternative splicing of the RAB6A gene, differing in only 3 amino acids near the PM3 GTP-binding domain; Rab6A' does not bind Rabkinesin-6 (a Rab6A effector) due to a single amino acid difference at position 87 (T vs A), and Rab6A' overexpression does not induce redistribution of Golgi proteins to ER as Rab6A does. Molecular cloning and sequencing of human RAB6A gene; GTP-binding assays; immunofluorescence; yeast two-hybrid interaction with Rabkinesin-6 and GAPCenA; GTP-bound mutant overexpression in HeLa cells Molecular biology of the cell High 11071909
2000 Rab6-KIFL (KIF20A) accumulates in mitotic cells at the spindle midzone during anaphase and at the cleavage furrow and midbody during telophase; microinjection of anti-Rab6-KIFL antibodies causes cytokinesis failure (binucleate cells) by defecting cleavage furrow formation. Immunofluorescence; time-lapse microscopy; microinjection of inhibitory antibodies; overexpression cytokinesis assay The EMBO journal High 11060022
2002 Rab6a' (but not Rab6a) is required for early/recycling endosome-to-TGN retrograde transport, working together with specific SNARE complexes (syntaxin 6, syntaxin 16, Vti1a with VAMP3/cellubrevin or VAMP4); Rab6a has been implicated in Golgi-to-ER transport. Permeabilized cell retrograde transport assay; identification of SNARE interactions; functional depletion/inhibition studies The Journal of cell biology High 11839770
2002 Dynactin binds specifically to Rab6 (but not to other Golgi Rabs) and shows Rab6-dependent recruitment to Golgi membranes; Rab6 acts as a specificity factor controlling dynactin recruitment to membranes. Pulldown assays; immunofluorescence; Golgi membrane recruitment assay with dominant-negative and active Rab6 mutants Current biology High 12401177
2002 Rab6IP2A and Rab6IP2B specifically interact with all three Rab6 isoforms (Rab6A, A', B); they are recruited to Golgi membranes in a Rab6:GTP-dependent manner; overexpression of the Rab6-binding domain of Rab6IP2 inhibits retrograde transport of Shiga toxin B subunit from plasma membrane to Golgi, suggesting Rab6IP2 functions in the Rab6A'-regulated pathway. Yeast two-hybrid screen; Golgi membrane recruitment assay; Shiga toxin retrograde transport assay Traffic Medium 11929610
2003 Phage display-derived recombinant antibodies specific to GTP-bound Rab6 revealed that Rab6 is in its GTP-bound conformation on the Golgi apparatus and on transport intermediates; Rab6 GTPase activity modulates the geometry/morphology of transport intermediates. Antibody phage display; intracellular expression of GFP-tagged conformation-specific antibodies; live-cell imaging Science High 12738866
2004 Both Rab6A and Rab6A' GTP-restricted mutants promote microtubule-dependent recycling of Golgi resident glycosylation enzymes to the ER with similar efficiency; this Rab6-directed Golgi-to-ER recycling requires functional dynactin (inhibited by p50/dynamitin overexpression or C-terminal Bicaudal-D fragment), and is initiated from the trans-Golgi network. siRNA knockdown; overexpression of GTP-restricted mutants; live imaging; p50/dynamitin dominant-negative overexpression Molecular biology of the cell High 15483056
2004 TMF/ARA160 is a Golgi golgin that binds to all three Rab6 isoforms; depletion of TMF by RNAi causes modest dispersal of Golgi membranes, indicating a role in Golgi organization. Co-immunoprecipitation; RNAi knockdown; immunofluorescence; sequence-based identification of conserved Rab6-binding motif BMC cell biology Medium 15128430
2006 Rab6A' (but not Rab6A) is required for cell cycle progression through mitosis; Rab6A' alteration blocks cells in metaphase with the Mad2-spindle checkpoint activated; the Rab6 effector p150(Glued) (dynactin subunit) remains associated with kinetochores; GAPCenA depletion produces a similar phenotype, suggesting Rab6A' regulates dynein/dynactin dynamics at kinetochores for the metaphase/anaphase transition. siRNA knockdown of Rab6A'; time-lapse microscopy; immunofluorescence for spindle checkpoint markers; co-depletion of GAPCenA The EMBO journal High 16395330
2006 Rab6A and Rab6A' perform non-overlapping functions: Rab6A' knockdown (but not Rab6A) hampers retrograde transport of Shiga Toxin B-subunit and causes defects in Golgi-associated protein recycling through the ER; Rab6A' is required for cell cycle progression through mitosis; Ile62 is a key residue uncoupling Rab6A' functions in mitosis versus retrograde trafficking. siRNA with isoform-specific oligonucleotides; Shiga Toxin B retrograde transport assay; cell cycle analysis; mutagenesis of Ile62 Traffic High 16536738
2007 Rab6 marks exocytotic vesicles and, together with kinesin-1, stimulates processive microtubule-based transport to the cell periphery; Rab6 directs targeting of secretory vesicles to plasma-membrane sites enriched in the cortical protein ELKS. Live-cell imaging; siRNA knockdown; co-immunoprecipitation; identification of ELKS as Rab6 effector; vesicle motility assays Developmental cell High 17681140
2007 TMF/ARA160 knockdown blocks retrograde transport of Shiga toxin from early/recycling endosomes to TGN and causes Rab6-dependent displacement of GalNAc-T2 (but not GalT) from the Golgi; the cytoplasmic region of GalNAc-T2 is critical for TMF-dependent Golgi retention. RNAi knockdown of TMF and Rab6; Shiga toxin retrograde transport assay; immunofluorescence; chimeric protein analysis Experimental cell research High 17698061
2007 Rab6 regulates two distinct retrograde Golgi trafficking pathways involving ZW10/RINT-1 and COG complexes; epistatic Rab6 depletion suppresses Golgi disruption caused by ZW10/RINT-1 or COG inactivation; BicaudalD C-terminal fragment (linking Rab6 to dynactin/dynein) suppresses ZW10 but not COG knockdown-induced disruption. siRNA epistasis experiments; dominant-negative Rab6 and BicaudalD expression; immunofluorescence; multiple depletion combinations Molecular biology of the cell High 17699596
2007 Rab6-interacting protein 1 (R6IP1) binds both Rab6 (GTP-bound) and Rab11A (GTP-bound); R6IP1 is targeted to the Golgi in a Rab6-dependent manner; overexpression of R6IP1 promotes Rab11A–Rab6 interaction (detected by FRET/FLIM) and accumulates recycling endosomes in the pericentriolar area; R6IP1 function is required during metaphase and cytokinesis. Co-immunoprecipitation; FRET/FLIM in live cells; subcellular localization; dominant-negative and siRNA experiments; cell cycle analysis Traffic High 17725553
2008 Rab6 GTPase interacts with gerodermia osteodysplastica protein SCYL1BP1 (GORAB); GORAB localizes to the Golgi apparatus; loss-of-function mutations in SCYL1BP1 cause gerodermia osteodysplastica, linking Rab6-associated secretory pathway abnormalities to this connective tissue disorder. Identification of disease mutations; co-localization studies; protein interaction assay Nature genetics Medium 18997784
2008 DYNLRB1 (dynein light chain) specifically interacts with all three Rab6 isoforms; DYNLRB1 shows preferred association with GTP-bound Rab6A and GDP-bound Rab6A'/Rab6B; DYNLRB1 co-localizes with Rab6 at the Golgi apparatus, representing the first direct interaction between Rab6 and the dynein complex. Yeast two-hybrid; co-immunoprecipitation; pulldown assays; immunofluorescence co-localization Cell motility and the cytoskeleton High 18044744
2008 Rab6a interacts with effectors BicaudalD2, p150(Glued), and PIST through their coiled-coil domains; all three bind GTP-bound Rab6a with Kd in high nanomolar to low micromolar range; BicaudalD2 and p150 binding moderately inhibits Rab6a intrinsic GTPase activity; effectors display rapid on- and off-rates (single-step binding kinetics). In vitro binding/biophysical assays (ITC, fluorescence); GTPase activity assays; transient kinetic analysis The Journal of biological chemistry High 19019823
2009 Crystal structure of Rab6a-GTP in complex with a 378-residue fragment of Rab6IP1 was solved at 3.2 Å; the first and last alpha-helices of the RUN domain of Rab6IP1 mediate binding to switch I, switch II, and interswitch region of Rab6; comparison with GCC185 complex reveals conformational flexibility in Rab6's hydrophobic triad mediates recognition of distinct effectors. X-ray crystallography; structural comparison with Rab6-GCC185 complex Structure High 19141279
2010 BICDR-1 is a Rab6 effector that interacts with kinesin Kif1C and the dynein/dynactin complex; BICDR-1 regulates pericentrosomal localization of Rab6-positive secretory vesicles and restricts anterograde secretory transport, inhibiting neuritogenesis in early neuronal development; BICDR-1 is required for neural development in zebrafish. Co-immunoprecipitation; live-cell imaging; siRNA knockdown; zebrafish knockdown; fluorescence microscopy The EMBO journal High 20360680
2011 Rab8A stably associates with exocytotic vesicles in a Rab6-dependent manner; Rab8A is required for docking and fusion of exocytotic carriers (not for budding or motility); Rab8A and ELKS act in the same pathway; MICAL3 links Rab8A and ELKS, and its monooxygenase activity is required for its own turnover and remodeling of vesicle-docking protein complexes. Live-cell imaging; siRNA knockdown; co-immunoprecipitation; dominant-negative MICAL3 expression; vesicle tracking Current biology High 21596566
2012 Human Ric1 and Rgp1 form a complex that acts as the guanine nucleotide exchange factor (GEF) for Rab6A, binding preferentially to GDP-bound Rab6A and catalyzing nucleotide exchange; Rab33B-GTP binds Ric1 at a distinct site, linking medial and late Golgi Rab proteins in a cascade; loss of Ric1 or Rgp1 destabilizes Rab6 and blocks Rab6-dependent retrograde transport of mannose-6-phosphate receptors. In vitro GEF nucleotide exchange assay; co-immunoprecipitation; siRNA knockdown with transport assay; binding assays The Journal of biological chemistry High 23091056
2012 Rab6 depletion by electron tomography reveals accumulation of two classes of coated vesicles (clathrin-coated and COPI-coated) at the trans-Golgi/TGN and a >50% increase in Golgi cisternal number; Rab6 is essential for trafficking of these vesicles, and Golgi-to-cell-surface transport is delayed. Electron tomography; siRNA knockdown; electron microscopy; VSV-G cargo transport kinetics Traffic High 22335553
2013 Rab6 depletion reduces TNF delivery to the cell surface in macrophages; Rab6-GFP localizes on TGN-derived tubular carriers marked by golgin p230; Rab6 depletion and inactive mutants alter tubular carrier egress and reduce p230 membrane association, suggesting Rab6 stabilizes p230 on tubular carriers to facilitate TNF transport. siRNA/shRNA knockdown; live-cell imaging; dominant-negative mutants; electron microscopy; TNF secretion ELISA PloS one High 23437303
2014 COH1 (VPS13B) association with the Golgi complex depends on Rab6; RAB6A/A' knockdown prevents COH1 Golgi localization; constitutively active RAB6_Q72L preferentially co-immunoprecipitates with COH1, identifying COH1 as a RAB6 effector; COH1 depletion in neurons impairs neurite outgrowth. RNAi knockdown of RAB6A/A'; co-immunoprecipitation with active/inactive RAB6 mutants; membrane solubilization; primary neuron knockdown with morphological readout The Journal of biological chemistry High 25492866
2015 KIF1C transports Rab6A-positive vesicles and can influence Golgi organization; KIF1C binds Rab6A directly both via its motor domain and C-terminus; Rab6A binding to the KIF1C motor domain inhibits microtubule interaction in vitro and in cells, decreasing the amount of motile KIF1C; KIF1C depletion slows protein delivery to the cell surface and causes Golgi fragmentation; KIF1C can protect Golgi membranes from fragmentation in the absence of an intact microtubule network, requiring both Rab6A-binding sites. In vitro microtubule binding assay; co-immunoprecipitation; siRNA knockdown; live-cell imaging; Golgi fragmentation assay; rescue experiments with binding-deficient mutants eLife High 25821985
2015 GORAB missense mutations (p.Ala220Pro and p.Ser175Phe) found in gerodermia osteodysplastica patients fall within an internal IGRAB domain that binds both RAB6 and ARF5; RAB6 and ARF5 bind GORAB via the same domain; p.Ala220Pro abolishes interaction with both RAB6 and ARF5 and causes cytoplasmic mislocalization; p.Ser175Phe selectively impairs ARF5 binding and displaces GORAB to vesicular structures. Yeast two-hybrid; co-immunoprecipitation; immunofluorescence; mutagenesis with Golgi targeting assay The Journal of investigative dermatology High 26000619
2015 BICD2 is a cytosolic factor required for Golgi targeting of Rab6A; BICD2 stabilizes GTP-bound Rab6A on Golgi membranes (FRAP shows reduced Rab6A exchange rate when BICD2 C-terminus is overexpressed); Rab6A and BICD2 are required for Golgi tubule fusion with ER in BFA-treated cells, confirming a role in COPI-independent Golgi-to-ER retrograde transport. Reconstitution of Golgi targeting in SLO-permeabilized HeLa cells; FRAP; BICD2 knockdown; BFA-induced Golgi-ER fusion assay Biochimica et biophysica acta High 25962623
2015 RAB6A knockout mice die at an early stage of embryonic development, establishing RAB6A as an essential gene; Rab6-depleted MEFs show altered Golgi morphology, reduced Golgi-associated levels of Bicaudal-D and myosin II, delayed VSV-G secretion, protection against ricin toxicity, and impaired cell growth. Conditional knockout mouse; 4-OHT-induced Cre-mediated deletion in MEFs; immunofluorescence; secretion assays; toxin sensitivity Biology of the cell High 26304202
2017 In melanocytes, the secretory pathway relies on RAB6 and its effector ELKS to directly transport and dock Golgi-derived carriers to melanosomes, delivering MART-1 and TYRP2/DCT cargo; this RAB6/ELKS-dependent pathway controls melanosome formation, maturation, and pigment synthesis; RAB6 KO mice display pigmentation defects. Live-cell imaging; siRNA knockdown; RAB6 KO mice; co-immunoprecipitation; cargo tracking to melanosomes Nature communications High 28607494
2018 Rab6-dependent retrograde traffic of the LAT adapter from the plasma membrane through the Golgi-TGN controls TCR stimulation and immune synapse formation; this retrograde transport of LAT also depends on Syntaxin-16; in vivo Rab6 KO CD4+ T cells show impaired TCR stimulation. siRNA/shRNA knockdown in human cells; Rab6 KO mouse T cells; immunofluorescence; TCR stimulation assays; in vivo T cell activation The Journal of experimental medicine High 29440364
2019 RAB6-positive post-Golgi carriers are the dominant class of secretory carriers regardless of cargo; RAB6 inactivation leads to broad reduction of protein secretion; exocytosis occurs at localized hotspots juxtaposed to focal adhesions, and the RAB6-dependent machinery plays an essential role in this spatial restriction. Synchronized secretion assay (RUSH system); live-cell imaging; RAB6 siRNA; tracking of multiple cargo types The Journal of cell biology High 31142554
2020 In presynaptic nerve terminals, ELKS1 (a stationary presynaptic protein with Golgin homology) captures Rab6-marked vesicular cargo via direct Rab6 binding; this capturing mechanism can be transferred to mitochondria by mistargeting ELKS1 or Rab6; ELKS1 and Rab6 KO experiments establish the capturing function. Knockout and rescue experiments for ELKS1 and Rab6; live-cell imaging in neurons; mistargeting experiments to mitochondria; co-immunoprecipitation Cell reports High 32521280
2021 Newly synthesized TrkB receptors traffic through the secretory pathway in Rab6-positive carriers; combined activity of kinesin-1 and kinesin-3 is required for the formation and processive anterograde transport of Rab6/TrkB axonal carriers; Rab6 regulates TrkB anterograde delivery into the axon. Microfluidic compartmental devices; inducible secretion assay (RUSH); live-cell imaging; siRNA knockdown of kinesins; hippocampal neuron cultures Developmental cell High 33571451
2022 RAB6A/A' and RAB6B double knockout impairs apical localization of CRB3 in apical radial glia cells and induces delamination and ectopic division; post-Golgi transport of RAB6+ vesicles occurs toward microtubule minus-ends and depends on dynein; dynein activator LIS1 knockout phenocopies RAB6 double KO; identifying a RAB6-dynein-LIS1 complex for Golgi-to-apical surface transport. In situ subcellular live imaging in developing neocortex; conditional double knockout; CRB3 localization assay; dynein inhibition; LIS1 knockout EMBO reports High 35979738
1999 Rab6 phosphorylation is induced in platelets by thrombin or phorbol esters via a PKC-dependent mechanism (blocked by Ro-31-8220); PKC phosphorylation of Rab6C increases GTP affinity ~3-fold and triggers translocation of Rab6 from platelet particulate fractions to cytosol, suggesting phosphorylation modulates Rab6 membrane association and functional interactions in vesicle trafficking. 32P metabolic labeling; PKC inhibitor studies; subcellular fractionation; in vitro phosphorylation and nucleotide binding assays with recombinant Rab6C The Biochemical journal High 10455022

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Early/recycling endosomes-to-TGN transport involves two SNARE complexes and a Rab6 isoform. The Journal of cell biology 445 11839770
1998 Interaction of a Golgi-associated kinesin-like protein with Rab6. Science (New York, N.Y.) 425 9438855
1999 Rab6 coordinates a novel Golgi to ER retrograde transport pathway in live cells. The Journal of cell biology 345 10562278
2007 Rab6 regulates transport and targeting of exocytotic carriers. Developmental cell 295 17681140
1994 The small GTP-binding protein rab6 functions in intra-Golgi transport. The Journal of cell biology 225 7798313
2000 The Rab6-binding kinesin, Rab6-KIFL, is required for cytokinesis. The EMBO journal 180 11060022
2002 The Rab6 GTPase regulates recruitment of the dynactin complex to Golgi membranes. Current biology : CB 172 12401177
2011 Rab6, Rab8, and MICAL3 cooperate in controlling docking and fusion of exocytotic carriers. Current biology : CB 161 21596566
1997 GTP-bound forms of rab6 induce the redistribution of Golgi proteins into the endoplasmic reticulum. Proceedings of the National Academy of Sciences of the United States of America 151 9050864
1999 A novel Rab6-interacting domain defines a family of Golgi-targeted coiled-coil proteins. Current biology : CB 136 10209123
2002 Characterization of novel Rab6-interacting proteins involved in endosome-to-TGN transport. Traffic (Copenhagen, Denmark) 132 11929610
2010 Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis. The EMBO journal 130 20360680
2008 Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin. Nature genetics 128 18997784
1999 Characterization of GAPCenA, a GTPase activating protein for Rab6, part of which associates with the centrosome. The EMBO journal 125 10202141
1993 A cytosolic complex of p62 and rab6 associates with TGN38/41 and is involved in budding of exocytic vesicles from the trans-Golgi network. The Journal of cell biology 124 8349729
2006 Rab6A and Rab6A' GTPases play non-overlapping roles in membrane trafficking. Traffic (Copenhagen, Denmark) 119 16536738
2009 Rab6 and Rab11 regulate Chlamydia trachomatis development and golgin-84-dependent Golgi fragmentation. PLoS pathogens 114 19816566
2003 Recombinant antibodies to the small GTPase Rab6 as conformation sensors. Science (New York, N.Y.) 105 12738866
2000 The small GTPase Rab6B, a novel Rab6 subfamily member, is cell-type specifically expressed and localised to the Golgi apparatus. Journal of cell science 105 10893188
1995 Two-hybrid system screen with the small GTP-binding protein Rab6. Identification of a novel mouse GDP dissociation inhibitor isoform and two other potential partners of Rab6. The Journal of biological chemistry 102 7782346
2000 Alternative splicing of the human Rab6A gene generates two close but functionally different isoforms. Molecular biology of the cell 97 11071909
1996 Mutation of the Rab6 homologue of Saccharomyces cerevisiae, YPT6, inhibits both early Golgi function and ribosome biosynthesis. The Journal of biological chemistry 96 8663225
2004 Regulation of microtubule-dependent recycling at the trans-Golgi network by Rab6A and Rab6A'. Molecular biology of the cell 94 15483056
1993 Identification of small GTP-binding rab proteins in human platelets: thrombin-induced phosphorylation of rab3B, rab6, and rab8 proteins. Proceedings of the National Academy of Sciences of the United States of America 93 8356066
2019 RAB6 and microtubules restrict protein secretion to focal adhesions. The Journal of cell biology 90 31142554
2000 Multiple aspects of Rab protein action in the secretory pathway: focus on Rab3 and Rab6. Biochimie 88 10865125
2004 TMF is a golgin that binds Rab6 and influences Golgi morphology. BMC cell biology 85 15128430
2007 Rab6 regulates both ZW10/RINT-1 and conserved oligomeric Golgi complex-dependent Golgi trafficking and homeostasis. Molecular biology of the cell 79 17699596
2007 Rab6-interacting protein 1 links Rab6 and Rab11 function. Traffic (Copenhagen, Denmark) 79 17725553
2014 Cohen syndrome-associated protein COH1 physically and functionally interacts with the small GTPase RAB6 at the Golgi complex and directs neurite outgrowth. The Journal of biological chemistry 76 25492866
2010 Rab33b and Rab6 are functionally overlapping regulators of Golgi homeostasis and trafficking. Traffic (Copenhagen, Denmark) 71 20163571
2009 Structural basis for recruitment of Rab6-interacting protein 1 to Golgi via a RUN domain. Structure (London, England : 1993) 70 19141279
2009 The COG complex, Rab6 and COPI define a novel Golgi retrograde trafficking pathway that is exploited by SubAB toxin. Traffic (Copenhagen, Denmark) 67 19678899
2006 A role for the Rab6A' GTPase in the inactivation of the Mad2-spindle checkpoint. The EMBO journal 67 16395330
1999 Rab6 is phosphorylated in thrombin-activated platelets by a protein kinase C-dependent mechanism: effects on GTP/GDP binding and cellular distribution. The Biochemical journal 67 10455022
1996 Identification and localization of rab6, separation of rab6 from ERD2 and implications for an 'unstacked' Golgi, in Plasmodium falciparum. Molecular and biochemical parasitology 66 9010846
1998 Rab6 regulation of rhodopsin transport in Drosophila. The Journal of biological chemistry 65 9685396
2008 Rab6 family proteins interact with the dynein light chain protein DYNLRB1. Cell motility and the cytoskeleton 64 18044744
2006 Transport of ricin from endosomes to the Golgi apparatus is regulated by Rab6A and Rab6A'. Traffic (Copenhagen, Denmark) 64 16683916
2012 Ric1-Rgp1 complex is a guanine nucleotide exchange factor for the late Golgi Rab6A GTPase and an effector of the medial Golgi Rab33B GTPase. The Journal of biological chemistry 63 23091056
2007 Rab6 mediates membrane organization and determinant localization during Drosophila oogenesis. Development (Cambridge, England) 63 17329360
2017 Routing of the RAB6 secretory pathway towards the lysosome related organelle of melanocytes. Nature communications 62 28607494
2012 Electron tomography reveals Rab6 is essential to the trafficking of trans-Golgi clathrin and COPI-coated vesicles and the maintenance of Golgi cisternal number. Traffic (Copenhagen, Denmark) 60 22335553
1994 Determination of structural requirements for the interaction of Rab6 with RabGDI and Rab geranylgeranyltransferase. The Journal of biological chemistry 60 8175798
1993 Rab6 is associated with a compartment that transports rhodopsin from the trans-Golgi to the site of rod outer segment disk formation in frog retinal photoreceptors. Journal of cell science 60 8308063
1996 Differential effects of a Rab6 mutant on secretory versus amyloidogenic processing of Alzheimer's beta-amyloid precursor protein. The Journal of biological chemistry 58 8576122
2015 miR-5100 promotes tumor growth in lung cancer by targeting Rab6. Cancer letters 57 25754817
2011 Characterization of Aspergillus nidulans RabC/Rab6. Traffic (Copenhagen, Denmark) 57 21226815
2007 Functional involvement of TMF/ARA160 in Rab6-dependent retrograde membrane traffic. Experimental cell research 57 17698061
2007 Rab6 is increased in Alzheimer's disease brain and correlates with endoplasmic reticulum stress. Neuropathology and applied neurobiology 54 17573808
2015 Rab6 regulation of the kinesin family KIF1C motor domain contributes to Golgi tethering. eLife 53 25821985
2007 Rab6 and the secretory pathway affect oocyte polarity in Drosophila. Development (Cambridge, England) 53 17827179
2012 RAB-6.2 and the retromer regulate glutamate receptor recycling through a retrograde pathway. The Journal of cell biology 52 22213799
2007 Regulation of anterograde transport of adrenergic and angiotensin II receptors by Rab2 and Rab6 GTPases. Cellular signalling 49 17716866
2013 Rab6a/a' are important Golgi regulators of pro-inflammatory TNF secretion in macrophages. PloS one 48 23437303
2013 Rab6 dependent post-Golgi trafficking of HSV1 envelope proteins to sites of virus envelopment. Traffic (Copenhagen, Denmark) 48 24152084
2020 Small GTPase RAB6 deficiency promotes alveolar progenitor cell renewal and attenuates PM2.5-induced lung injury and fibrosis. Cell death & disease 45 33012781
2018 Rab6-dependent retrograde traffic of LAT controls immune synapse formation and T cell activation. The Journal of experimental medicine 45 29440364
2016 Rab6 Is Required for Multiple Apical Transport Pathways but Not the Basolateral Transport Pathway in Drosophila Photoreceptors. PLoS genetics 43 26890939
2008 Biophysical analysis of the interaction of Rab6a GTPase with its effector domains. The Journal of biological chemistry 43 19019823
2004 Rab6 membrane association is dependent of Presenilin 1 and cellular phosphorylation events. Brain research. Molecular brain research 43 14992812
1994 The effector domain of Rab6, plus a highly hydrophobic C terminus, is required for Golgi apparatus localization. Molecular and cellular biology 43 8264642
2009 Intracellular phospholipase A1gamma (iPLA1gamma) is a novel factor involved in coat protein complex I- and Rab6-independent retrograde transport between the endoplasmic reticulum and the Golgi complex. The Journal of biological chemistry 42 19632984
2006 The Rab6 effector Bicaudal D1 associates with Chlamydia trachomatis inclusions in a biovar-specific manner. Infection and immunity 42 17101644
2007 Giantin interacts with both the small GTPase Rab6 and Rab1. Experimental cell research 40 17475246
2012 Involvement of Rab6 in the regulation of phagocytosis against virus infection in invertebrates. Journal of proteome research 39 22928698
2009 The localization of the Golgin GCC185 is independent of Rab6A/A' and Arl1. Cell 37 19703403
2005 Rab6 interacts with the mint3 adaptor protein. Biological chemistry 35 16207088
2020 ELKS1 Captures Rab6-Marked Vesicular Cargo in Presynaptic Nerve Terminals. Cell reports 34 32521280
2011 A role for the small GTPase Rab6 in assembly of human cytomegalovirus. Journal of virology 34 21411515
2022 RAB6 and dynein drive post-Golgi apical transport to prevent neuronal progenitor delamination. EMBO reports 33 35979738
2015 Phenotypic characterisation of RAB6A knockout mouse embryonic fibroblasts. Biology of the cell 33 26304202
2002 Toxoplasma gondii Rab6 mediates a retrograde pathway for sorting of constitutively secreted proteins to the Golgi complex. The Journal of biological chemistry 32 12468555
2011 Rich regulates target specificity of photoreceptor cells and N-cadherin trafficking in the Drosophila visual system via Rab6. Neuron 31 21835342
2015 GORAB Missense Mutations Disrupt RAB6 and ARF5 Binding and Golgi Targeting. The Journal of investigative dermatology 29 26000619
2017 MiR-5100 increases the cisplatin resistance of the lung cancer stem cells by inhibiting the Rab6. Molecular carcinogenesis 27 29144562
2003 Evidence that the transport of ricin to the cytoplasm is independent of both Rab6A and COPI. Journal of cell science 27 12865434
2021 Combined kinesin-1 and kinesin-3 activity drives axonal trafficking of TrkB receptors in Rab6 carriers. Developmental cell 26 33571451
2016 The role of Rab6a and phosphorylation of non-muscle myosin IIA tailpiece in alcohol-induced Golgi disorganization. Scientific reports 26 27535804
2015 Reconstitution of the targeting of Rab6A to the Golgi apparatus in semi-intact HeLa cells: A role of BICD2 in stabilizing Rab6A on Golgi membranes and a concerted role of Rab6A/BICD2 interactions in Golgi-to-ER retrograde transport. Biochimica et biophysica acta 25 25962623
2014 The trials and tubule-ations of Rab6 involvement in Golgi-to-ER retrograde transport. Biochemical Society transactions 25 25233431
2014 Distinct sets of Rab6 effectors contribute to ZW10--and COG-dependent Golgi homeostasis. Traffic (Copenhagen, Denmark) 23 24575842
2018 Rab6 promotes insulin receptor and cathepsin trafficking to regulate autophagy induction and activity in Drosophila. Journal of cell science 22 30111579
2012 Rab6 is a modulator of the unfolded protein response: implications for Alzheimer's disease. Journal of Alzheimer's disease : JAD 22 22124028
2012 Rab6 is required for the exocytosis of cortical granules and the recruitment of separase to the granules during the oocyte-to-embryo transition in Caenorhabditis elegans. Journal of cell science 22 22992455
2009 Structural aspects of Rab6-effector complexes. Biochemical Society transactions 22 19754447
1997 Small GTP-binding protein, Rab6, is associated with secretory granules in atrial myocytes. The American journal of physiology 22 9176151
2000 Identification of Rab6 as an N-ethylmaleimide-sensitive fusion protein-binding protein. The Biochemical journal 21 11062069
1996 Transport between cis and medial Golgi cisternae requires the function of the Ras-related protein Rab6. The Journal of biological chemistry 21 8663167
2016 Involvement of Rab6a in organelle rearrangement and cytoskeletal organization during mouse oocyte maturation. Scientific reports 20 27030207
2002 WTH3, a new member of the Rab6 gene family, and multidrug resistance. Biochimica et biophysica acta 20 12007787
2016 ARHGEF10 directs the localization of Rab8 to Rab6-positive executive vesicles. Journal of cell science 18 27550519
2013 Targeting of the small GTPase Rab6A' by the Legionella pneumophila effector LidA. Infection and immunity 18 23569112
2012 Rab6-mediated retrograde transport regulates inner nuclear membrane targeting of caveolin-2 in response to insulin. Traffic (Copenhagen, Denmark) 17 22607032
2020 Rab6 regulates recycling and retrograde trafficking of MR1 molecules. Scientific reports 16 33247182
2018 The Biological Activity of AAV Vectors for Choroideremia Gene Therapy Can Be Measured by In Vitro Prenylation of RAB6A. Molecular therapy. Methods & clinical development 16 29707603
2005 Assay and functional properties of Rabkinesin-6/Rab6-KIFL/MKlp2 in cytokinesis. Methods in enzymology 16 16473625
2017 Involvement of ARHGEF10, GEF for RhoA, in Rab6/Rab8-mediating membrane traffic. Small GTPases 15 28448737
1995 Nucleotide induced conformation determines posttranslational isoprenylation of the ras related rab6 protein in insect cells. FEBS letters 15 8521955
2020 A rice small GTPase, Rab6a, is involved in the regulation of grain yield and iron nutrition in response to CO2 enrichment. Journal of experimental botany 14 32525991