The Rab6 subfamily of small GTPases consists of three different isoforms: Rab6A, Rab6A′ and Rab6B. Both Rab6A and Rab6A′ are ubiquitously expressed whereas Rab6B is predominantly expressed in brain. Recent studies have shown that Rab6A′ is the isoform regulating the retrograde transport from late endosomes via the Golgi to the ER and in the transition from anaphase to metaphase during mitosis. Since the role of Rab6B is still ill defined, we set out to characterize its intracellular environment and dynamic behavior. In a Y-2H search for novel Rab6 interacting proteins, we identified Bicaudal-D1, a large coiled-coil protein known to bind to the dynein/dynactin complex and previously shown to be a binding partner for Rab6A/Rab6A′. Co-immunoprecipitation studies and pull down assays confirmed that Bicaudal-D1 also interacts with Rab6B in its active form. Using confocal laser scanning microscopy it was established that Rab6B and Bicaudal-D1 co-localize at the Golgi and vesicles that align along microtubules. Furthermore, both proteins co-localized with dynein in neurites of SK-N-SH cells. Live cell imaging revealed bi-directional movement of EGFP-Rab6B structures in SK-N-SH neurites. We conclude from our data that the brain-specific Rab6B via Bicaudal-D1 is linked to the dynein/dynactin complex, suggesting a regulatory role for Rab6B in the retrograde transport of cargo in neuronal cells.

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Experimental Cell Research: emphasizing molecular approaches to cell biology
Erasmus MC: University Medical Center Rotterdam

Wanschers, B., van de Vorstenbosch, R., Schlager, M., Splinter, D., Akhmanova, A., Hoogenraad, C., … Fransen, J. (2007). A role for the Rab6B Bicaudal-D1 interaction in retrograde transport in neuronal cells. Experimental Cell Research: emphasizing molecular approaches to cell biology, 313(16), 3408–3420. doi:10.1016/j.yexcr.2007.05.032