title: The small GTPase Rab6B, a novel Rab6 subfamily member, is cell-type specifically expressed and localised to the Golgi apparatus.
abstract: 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 endoplasmic reticulum (ER). Here, we report on the identification of a Rab6 isoform, termed Rab6B. The corresponding full-length cDNA was isolated from a Caco-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 independent gene which is located on chromosome 3 region q21-q23. In contrast to Rab6A whose expression is ubiquitous, northern blot analysis, immunohistochemistry, and immunofluorescence demonstrated that Rab6B is expressed in a tissue 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 specifically expressed in microglia, pericytes and Purkinje cells. Endogenous Rab6B localises to the Golgi apparatus and to ERGIC-53-positive vesicles. Comparable studies between Rab6A and Rab6B revealed distinct biochemical and cellular properties. Rab6B displayed lower GTP-binding activities and in overexpression studies, the protein is distributed over Golgi and ER membranes, whereas Rab6A is more restricted to the Golgi apparatus. Since the GTP-bound form of Rab6B (Rab6B Q72L) does interact with all known Rab6A effectors, including Rabkinesin-6, the results suggest a cell-type specific role for Rab6B in retrograde membrane traffic at the level of the Golgi complex.
authors.affiliation: Department of Cell Biology, Institute of Cellular Signalling, University of Nijmegen, PO Box 9101, Nijmegen, The Netherlands.
authors.forename: F J
authors.initials: FJ
authors.lastname: Opdam
authors.forename: A
authors.initials: A
authors.lastname: Echard
authors.forename: H J
authors.initials: HJ
authors.lastname: Croes
authors.forename: J A
authors.initials: JA
authors.lastname: van den Hurk
authors.forename: R A
authors.initials: RA
authors.lastname: van de Vorstenbosch
authors.forename: L A
authors.initials: LA
authors.lastname: Ginsel
authors.forename: B
authors.initials: B
authors.lastname: Goud
authors.forename: J A
authors.initials: JA
authors.lastname: Fransen
mesh_terms: D000818:Animals; D001483:Base Sequence; D001692:Biological Transport / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000201:enzymology; D019556:COS Cells; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D020558:GTP Phosphohydrolases / Q000032:analysis / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006056:Golgi Apparatus / Q000201:enzymology*; D019073:HT29 Cells; D006801:Humans; D016547:Kinesins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D009474:Neurons / Q000201:enzymology; D017386:Sequence Homology, Amino Acid; D020691:rab GTP-Binding Proteins / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism
chemical_list: C410089:KIF20A protein, human; C094135:Rab6 protein; D020558:GTP Phosphohydrolases; D016547:Kinesins; D020691:rab GTP-Binding Proteins