Ng Ee Ling, Ng Jun Jie, Liang Fengyi, Tang Bor Luen
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
J Cell Physiol. 2009 Dec;221(3):716-28. doi: 10.1002/jcp.21911.
The expression profile and functions of the brain-enriched Rab22B/Rab31 small GTPase had remained uncharacterized. Using specific antibodies against Rab22B, we found the protein to be exceptionally enriched in nestin and RC2-positive radial glia of the embryonic mouse brain. In the adult brain, Rab22B is rather specifically expressed in glial fibrillary acidic protein (GFAP)-positive mature astrocytes, but is not clearly detectable in either 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)-positive mature oligodendrocytes or betaIII-tubulin (TuJ)-positive neurons. In probing for specific functions of Rab22B, we found that Rab22B silencing in A431 cells resulted in abnormal trafficking of the epidermal growth factor receptor (EGFR), Texas-red-labeled EGF, and the cation-independent mannose 6-phosphate receptor (M6PR). Affinity pull-down assays and co-immunoprecipitation analysis indicated that Rab22B could associate with EGFR in a GTP-dependent manner. Rab22B is thus a Rab protein specifically expressed in the astroglia lineage and may have a role in regulating EGFR trafficking in some cell types. Given that EGFR signaling modulates astrocyte development and oncogenesis of multiple cell types, Rab22B may thus have specific developmental or pathophysiological roles in cell types which it is enriched in.
在大脑中高度表达的Rab22B/Rab31小GTP酶的表达谱和功能一直未得到明确描述。我们使用针对Rab22B的特异性抗体，发现该蛋白在胚胎小鼠大脑中巢蛋白和RC2阳性的放射状胶质细胞中异常富集。在成体大脑中，Rab22B相当特异性地表达于胶质纤维酸性蛋白（GFAP）阳性的成熟星形胶质细胞中，但在2'，3'-环核苷酸3'-磷酸二酯酶（CNPase）阳性的成熟少突胶质细胞或βIII-微管蛋白（TuJ）阳性的神经元中均未清晰检测到。在探究Rab22B的特定功能时，我们发现Rab22B在A431细胞中的沉默导致表皮生长因子受体（EGFR）、德克萨斯红标记的表皮生长因子（EGF）和不依赖阳离子的甘露糖6-磷酸受体（M6PR）的转运异常。亲和下拉试验和免疫共沉淀分析表明，Rab22B可以以GTP依赖的方式与EGFR结合。因此，Rab22B是一种在星形胶质细胞谱系中特异性表达的Rab蛋白，可能在某些细胞类型中调节EGFR的转运。鉴于EGFR信号传导调节星形胶质细胞的发育和多种细胞类型的肿瘤发生，Rab22B可能在其富集的细胞类型中具有特定的发育或病理生理作用。
