The small GTPase Rab6B, a novel Rab6 subfamily member, is cell-type specifically expressed and localised to the Golgi apparatus.
The small GTPase Rab6B, a novel Rab6 subfamily member, is cell-type specifically expressed and localised to the Golgi apparatus.
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发表时间：
2000-08
影响因子：
4
通讯作者：
F. Opdam;Arnaud Echard;H. Croes;J.A.J.M. van den Hurk;R. A. V. D. Vorstenbosch;L. Ginsel;B. Goud;Jack A.M. Fransen
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作者：
F. Opdam;Arnaud Echard;H. Croes;J.A.J.M. van den Hurk;R. A. V. D. Vorstenbosch;L. Ginsel;B. Goud;Jack A.M. Fransen
小gtpase的Rab亚家族成员在细胞内运输途径的调节中发挥重要作用。Rab6A已被证明是一个从高尔基体到内质网（ER）的膜交通调节剂。在这里，我们报告了Rab6亚型的鉴定，称为Rab6B。从Caco-2细胞文库中分离到相应的全长cDNA。推导出的氨基酸序列与Rab6A蛋白的同源性为91%，序列差异分布在cooh末端结构域的大片区域。Rab6B由位于染色体3区q21-q23的一个独立基因编码。与Rab6A的普遍表达不同，northern blot分析、免疫组织化学和免疫荧光显示Rab6B的表达具有组织和细胞特异性。Rab6B主要在脑和神经母细胞瘤细胞系SK-N-SH中表达。在脑组织中，Rab6B在小胶质细胞、周细胞和浦肯野细胞中特异性表达。内源性Rab6B定位于高尔基体和ergic -53阳性囊泡。Rab6A和Rab6B之间的比较研究显示出不同的生化和细胞特性。Rab6B显示出较低的gtp结合活性，在过表达研究中，该蛋白分布在高尔基体和内质网膜上，而Rab6A则更多地局限于高尔基体。由于Rab6B的gtp结合形式（Rab6B Q72L）与所有已知的Rab6A效应物（包括Rabkinesin-6）相互作用，结果表明Rab6B在高尔基复合物水平的逆行膜运输中具有细胞类型特异性作用。
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.