The small GTPase Rab6B, a novel Rab6 subfamily member, is cell-type specifically expressed and localised to the Golgi apparatus

Members of the Rab subfamily of small GTPases play an important role in the regulation of intracellular transport routes. Rab6A has been shown to be a regulator of membrane traffic from the Golgi apparatus towards the endopla smic reticulum (ER), Here, we report on the identification of a Rab6 isofor m, termed Rab6B, The corresponding full-length cDNA was isolated from a Cac o-2 cell library. The deduced amino acid sequence showed 91% identity with the Rab6A protein and revealed that sequence divergence is dispersed over a large region of the COOH-terminal domain. Rab6B is encoded by an independe nt gene which is located on chromosome 3 region q21-q23. In contrast to Rab 6A whose expression is ubiquitous, northern blot analysis, immunohistochemi stry, and immunofluorescence demonstrated that Rab6B is expressed in a tiss ue and cell-type specific manner. Rab6B is predominantly expressed in brain and the neuroblastoma cell line SK-N-SH, In brain, Rab6B was found to be s pecifically expressed in microglia, pericytes and Purkinje cells. Endogenou s Rab6B localises to the Golgi apparatus and to ERGIC-53-positive vesicles. Comparable studies between Rab6A and Rab6B revealed distinct biochemical a nd cellular properties. Rab6B displayed lower GTP-binding activities and in overexpression studies, the protein is distributed over Golgi and ER membr anes, whereas Rab6A is more restricted to the Golgi apparatus. Since the GT P-bound form of Rab6B (Rab6B Q72L) does interact with all known Rab6A effec ters, including Rabkinesin-6, the results suggest a cell-type specific role for Rab6B in retrograde membrane traffic at the level of the Golgi complex .