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Gene Review

Rab6a  -  RAB6A, member RAS oncogene family

Mus musculus

Synonyms: 2610028L11Rik, AA419671, MNCb-1660, Rab-6, Rab6, ...
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Disease relevance of Rab6

  • When a dominant-negative Rab4 mutant or a constitutively active GTP-bound Rab6a protein was overexpressed in prion-infected neuroblastoma N2a cells, there was a marked increase of PrP(Sc) formation [1].

High impact information on Rab6

  • ERC1a and ERC1b/2 likely perform similar functions at distinct localizations, indicating unexpected connections between nonneuronal membrane traffic at the Golgi complex executed via Rab6 and neuronal membrane traffic at the active zone executed via RIMs [2].
  • One such protein, Rab6, is associated with the Golgi apparatus and has a C-terminal CXC motif that is geranylgeranylated on both cysteines [3].
  • To further characterize these two Ag presentation pathways, we altered the intra-Golgi transport of newly synthesized MHC class II by stably overexpressing, in B cells, mutants of a small G protein involved in the intra-Golgi transport, Rab6 [4].
  • Using a two-hybrid system screen of a mouse brain cDNA library, we have isolated several clones encoding proteins that interact with Rab6 [5].
  • Using immunocytochemistry (laser scanning confocal microscopy, immunoelectron microscopy), fractionation and immunoisolation methods, we show that during the early phase of synaptogenesis, Rab6p is associated with synaptophysin-containing membranes of a trans-Golgi subcompartment, post-Golgi vesicles and small synaptic vesicles or their precursors [6].

Biological context of Rab6


Anatomical context of Rab6

  • Rab6 GTPase regulates intracellular transport at the level of the Golgi complex [8].
  • In contrast, the retrograde transport of the Shiga toxin B subunit between the plasma membrane and the Golgi complex is partly inhibited in cells overexpressing the Rab6-binding domain of Rab6IP2 [8].
  • We show that in fibroblasts, Rab6 membrane association is PKC dependent, an effect strongly potentiated by inhibition of calcineurin [7].
  • To identify intracellular organelles involved in PrP(Sc) formation, we studied the role of the Ras-related GTP-binding proteins Rab4 and Rab6a in intracellular trafficking of the prion protein and production of PrP(Sc) [1].
  • However, at late stages, the association of Rab6p to small synaptic vesicles sharply decreases and its level of expression plateaus [6].

Associations of Rab6 with chemical compounds

  • Rap1 and Rab6 but not Ras from perillyl alcohol-treated NIH3T3 cells accumulated in the aqueous phase [9].
  • In this study, we demonstrate that unprenylated Rab6 could be detected in J774 cells after treatment with 3-PEHPC or risedronate for as little as 4 h, and reached 50% after 24 h [10].

Other interactions of Rab6

  • Moreover, we demonstrate that this regulation of Rab6 membrane association is dependent on PS1 [7].


  1. Stimulation of PrP(C) retrograde transport toward the endoplasmic reticulum increases accumulation of PrP(Sc) in prion-infected cells. Béranger, F., Mangé, A., Goud, B., Lehmann, S. J. Biol. Chem. (2002) [Pubmed]
  2. A family of RIM-binding proteins regulated by alternative splicing: Implications for the genesis of synaptic active zones. Wang, Y., Liu, X., Biederer, T., Südhof, T.C. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  3. The effector domain of Rab6, plus a highly hydrophobic C terminus, is required for Golgi apparatus localization. Beranger, F., Paterson, H., Powers, S., de Gunzburg, J., Hancock, J.F. Mol. Cell. Biol. (1994) [Pubmed]
  4. New evidence for two MHC class II-restricted antigen presentation pathways by overexpression of a small G protein. Briken, V., Lankar, D., Bonnerot, C. J. Immunol. (1997) [Pubmed]
  5. 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. Janoueix-Lerosey, I., Jollivet, F., Camonis, J., Marche, P.N., Goud, B. J. Biol. Chem. (1995) [Pubmed]
  6. The small GTP-binding protein, Rab6p, is associated with both Golgi and post-Golgi synaptophysin-containing membranes during synaptogenesis of hypothalamic neurons in culture. Tixier-Vidal, A., Barret, A., Picart, R., Mayau, V., Vogt, D., Wiedenmann, B., Goud, B. J. Cell. Sci. (1993) [Pubmed]
  7. Rab6 membrane association is dependent of Presenilin 1 and cellular phosphorylation events. Scheper, W., Zwart, R., Baas, F. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  8. Characterization of novel Rab6-interacting proteins involved in endosome-to-TGN transport. Monier, S., Jollivet, F., Janoueix-Lerosey, I., Johannes, L., Goud, B. Traffic (2002) [Pubmed]
  9. Inhibition of type I and type II geranylgeranyl-protein transferases by the monoterpene perillyl alcohol in NIH3T3 cells. Ren, Z., Elson, C.E., Gould, M.N. Biochem. Pharmacol. (1997) [Pubmed]
  10. Phosphonocarboxylate inhibitors of Rab geranylgeranyl transferase disrupt the prenylation and membrane localization of Rab proteins in osteoclasts in vitro and in vivo. Coxon, F.P., Ebetino, F.H., Mules, E.H., Seabra, M.C., McKenna, C.E., Rogers, M.J. Bone (2005) [Pubmed]
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