Guo Anchen, Wang Ting, Ng Ee Ling, Aulia Selina, Chong Kooi Hoong, Teng Felicia Yu Hsuan, Wang Ya, Tang Bor Luen
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
J Neurosci Res. 2006 May 1;83(6):1118-27. doi: 10.1002/jnr.20788.
The gene mutated in the mouse open brain (opb) phenotype antagonizes sonic hedgehog-mediated signaling and encodes a small GTPase of the Rab family, Rab23. To date, the brain expression profile and exact mechanism of function of the Rab23 protein has remained unknown. Specific antibodies generated against Rab23 showed that the protein is highly enriched in the adult rodent brain and present in low levels in multiple tissues of the adult rodent. Rab23 is found in the cytosol as well as being associated with the plasma and endosomal membranes. In the adult mouse brain, Rab23 is found in betaIII tubulin (TuJ) positive neuronal cell bodies and are most prominent in the cortex, hypothalamus and the cerebellum. It is, however, absent from glial fibrillary acidic protein (GFAP) positive astrocytes or CNPase positive oligodendrocytes. Despite the plasma membrane/endosomal membrane localization of Rab23, neither overexpression of the GTP-restricted nor the GDP-bound mutant forms affect internalization of transferrin or epidermal growth factor. Exogenous overexpression of Rab23 or its mutants also did not affect the morphological differentiation of thalamic neurons in culture. Expression of Rab23 in the adult brain is suggestive, however, of having a postnatal function beyond its role in embryonic development.
在小鼠开放性脑（opb）表型中发生突变的基因可拮抗音猬因子介导的信号传导，并编码Rab家族的一种小GTP酶Rab23。迄今为止，Rab23蛋白的脑表达谱和确切功能机制仍不清楚。针对Rab23产生的特异性抗体表明，该蛋白在成年啮齿动物脑中高度富集，而在成年啮齿动物的多种组织中含量较低。Rab23存在于细胞质中，也与质膜和内体膜相关。在成年小鼠脑中，Rab23存在于βIII微管蛋白（TuJ）阳性的神经元细胞体中，在皮质、下丘脑和小脑中最为突出。然而，在胶质纤维酸性蛋白（GFAP）阳性的星形胶质细胞或2',3'-环核苷酸3'-磷酸二酯酶（CNPase）阳性的少突胶质细胞中不存在。尽管Rab23定位于质膜/内体膜，但GTP限制型或GDP结合型突变体形式的过表达均不影响转铁蛋白或表皮生长因子的内化。Rab23或其突变体的外源性过表达也不影响培养的丘脑神经元的形态分化。然而，Rab23在成年脑中的表达表明其在出生后具有超越胚胎发育作用的功能。
