HGNC Approved Gene Symbol: RAB6B
Cytogenetic location: 3q22.1 Genomic coordinates (GRCh38): 3:133,824,235-133,895,882 (from NCBI)
RAB6B is a member of the large RAB subfamily of small GTPases that play important roles in the regulation of intracellular transport routes (Opdam et al., 2000).
Using RT-PCR with primers corresponding to conserved RAB domains involved in GTP-binding in colorectal adenocarcinoma cells, Opdam et al. (2000) cloned RAB6B. The deduced 207-amino acid protein is 91% identical to RAB6A (179513), with most differences in the C termini. RAB6B contains 6 conserved motifs involved in GTP-binding and a CxC motif involved in prenylation. Northern blot analysis detected 1.35-, 3.1-, and 5.6-kb transcripts predominantly in human brain and in a human neuroblastoma cell line. Immunoblot analysis showed expression of a 23-kD protein. Immunohistochemical analysis demonstrated expression in perinuclear regions and Golgi apparatus in neuroblastoma cells. In human brain, RAB6B was expressed in microglia, pericytes, and Purkinje cells.
Using GTP-binding assays, Opdam et al. (2000) found that RAB6B had lower binding activity than RAB6A. Both proteins colocalized at the Golgi complex. Yeast 2-hybrid analysis showed that RAB6B, like RAB6A, interacted with KIF20A (605664) and GAPCENA (RABGAP1; 615882). Opdam et al. (2000) concluded that RAB6B exerts a cell-type specific function in neuronal cells.
By yeast 2-hybrid, coimmunoprecipitation, and pull-down analyses, Wanschers et al. (2007) showed that RAB6B interacted with bicaudal D1 (BICD1; 602204). Confocal microscopy demonstrated colocalization of RAB6B and BICD1 at the Golgi and vesicles that align along microtubules, and both proteins colocalized with dynein (see 600112) in neurites of neuroblastoma cells. Wanschers et al. (2007) concluded that RAB6B via BICD1 is linked to the dynein/dynactin (see 601143) complex, suggesting a regulatory role for RAB6B in the retrograde transport of cargo in neuronal cells.
Using protein pull-down assays, Schlager et al. (2010) found that mouse Bicdr1 (BICDL1; 617002) showed strongest interaction with Rab6b, followed by Rab6a, with little binding to other Rabs tested. In a yeast 2-hybrid assay, the C-terminal region of Bicdr1 encompassing the second coiled-coil domain bound to constitutively active, GTPase-deficient Rab6a, but not to inactive, GDP-locked Rab6a. Overexpression of Bicdr1 in human and monkey epithelial cells caused accumulation of Bicdr1 in the pericentrosomal region along with Rab6-positive vesicles. In early cultures of mouse hippocampal neurons, Bicdr1 accumulated Rab6- and Npy (162640)-positive secretory vesicles around the centrosome in a dose-dependent manner, restricted anterograde secretory transport, and inhibited neurite outgrowth. Schlager et al. (2010) concluded that RAB6 and BICDR1 function in retrograde transport of secretory vesicles.
Garcia-Saez et al. (2006) determined the crystal structure of RAB6B in its active and inactive forms at 1.8- and 2.3-angstrom resolution, respectively.
By radiation hybrid analysis, Opdam et al. (2000) mapped the RAB6B gene to chromosome 3q21-q23.
Gross (2014) mapped the RAB6B gene to chromosome 3q22.1 based on an alignment of the RAB6B sequence (GenBank AF498940) with the genomic sequence (GRCh37).
Garcia-Saez, I., Tcherniuk, S., Kozielski, F. The structure of human neuronal Rab6B in the active and inactive form. Acta Crystallogr. D Biol. Crystallogr. 62: 725-733, 2006. [PubMed: 16790928] [Full Text: https://doi.org/10.1107/S0907444906015319]
Gross, M. B. Personal Communication. Baltimore, Md. 6/25/2014.
Opdam, F. J. M., Echard, A., Croes, H. J. E., van den Hurk, J. A. J. M., van de Vorstenbosch, R. A., Ginsel, L. A., Goud, B., Fransen, J. A. M. The small GTPase Rab6B, a novel Rab6 subfamily member, is cell-type specifically expressed and localised to the Golgi apparatus. J. Cell Sci. 113: 2725-2735, 2000. [PubMed: 10893188] [Full Text: https://doi.org/10.1242/jcs.113.15.2725]
Schlager, M. A., Kapitein, L. C., Grigoriev, I., Burzynski, G. M., Wulf, P. S., Kiejzer, N., de Graaff, E., Fukuda, M., Shepherd, I. T., Akhmanova, A., Hoogenraad, C. C. Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis. EMBO J. 29: 1637-1651, 2010. [PubMed: 20360680] [Full Text: https://doi.org/10.1038/emboj.2010.51]
Wanschers, B. F. J., van de Vorstenbosch, R., Schlager, M. A., Splinter, D., Akhmanova, A., Hoogenraad, C. C., Wieringa, B., Fransen, J. A. M. A role for the Rab6B Bicaudal-D1 interaction in retrograde transport in neuronal cells. Exp. Cell Res. 313: 3408-3420, 2007. [PubMed: 17707369] [Full Text: https://doi.org/10.1016/j.yexcr.2007.05.032]