Cleary M A, Uboha N, Picciotto M R, Beech R D
Department of Psychiatry, Yale University School of Medicine, 300 George Street, 8304, New Haven, CT 06511, USA.
Neuroscience. 2006 Dec;143(3):851-61. doi: 10.1016/j.neuroscience.2006.08.028. Epub 2006 Sep 22.
Ezrin is a member of the ERM (ezrin-radixin-moesin) family of membrane-cytoskeletal linking proteins. ERM proteins are involved in a wide variety of cellular functions including cell motility, signal transduction, cell-cell interaction and cell-matrix recognition. A recent in situ hybridization study showed that the mRNA encoding ezrin is expressed in neurogenic regions of the mature brain including the subventricular zone (SVZ) and rostral migratory stream (RMS); however, the specific cell types expressing ezrin and their relationship to migrating and proliferating cells in these regions have not been characterized previously. In this study, we used immunocytochemistry to perform double labeling with a variety of cell-type specific markers to characterize the expression of ezrin in the SVZ and RMS of adult mice. Ezrin was expressed at high levels in both the SVZ and RMS where ezrin-immunopositive processes formed a trabecular network surrounding the proliferating and migrating cells. Ezrin-positive cells co-labeled with the glial makers S100beta and GFAP (glial fibrillary acidic protein), but only minimally with the early neuronal markers beta III tubulin and polysialylated form of neural cell adhesion molecule 1 (PSA-NCAM), indicating that ezrin was expressed primarily in the glial tube cells. Ezrin positive cells also expressed beta-catenin, a membrane-complex protein previously implicated in the regulation of stem-cell proliferation and neuronal migration. Glial tube cells act as both precursors of, and a physical channel for, migrating neuroblasts. Bi-directional signals between glial tube cells and migrating neuroblasts have been shown to regulate the rates of both proliferation of the precursor cells and migration of the newly generated neuroblasts. Our finding that ezrin and beta-catenin are both present at the cell membrane of the glial tube cells suggests that these proteins may be involved in those signaling processes.
埃兹蛋白是膜细胞骨架连接蛋白的ERM(埃兹蛋白-根蛋白-膜突蛋白)家族成员。ERM蛋白参与多种细胞功能,包括细胞运动、信号转导、细胞间相互作用以及细胞与基质的识别。最近一项原位杂交研究表明,编码埃兹蛋白的mRNA在成熟大脑的神经发生区域表达,包括脑室下区(SVZ)和嘴侧迁移流(RMS);然而,之前尚未对表达埃兹蛋白的特定细胞类型及其与这些区域中迁移和增殖细胞的关系进行表征。在本研究中,我们使用免疫细胞化学方法,用多种细胞类型特异性标志物进行双重标记,以表征成年小鼠SVZ和RMS中埃兹蛋白的表达情况。埃兹蛋白在SVZ和RMS中均高水平表达,其中埃兹蛋白免疫阳性的突起形成围绕增殖和迁移细胞的小梁网络。埃兹蛋白阳性细胞与胶质细胞标志物S100β和胶质纤维酸性蛋白(GFAP)共标记,但与早期神经元标志物βIII微管蛋白和神经细胞黏附分子1的多唾液酸化形式(PSA-NCAM)的共标记极少,这表明埃兹蛋白主要在胶质管细胞中表达。埃兹蛋白阳性细胞还表达β-连环蛋白,一种先前与干细胞增殖和神经元迁移调控有关的膜复合蛋白。胶质管细胞既是迁移神经母细胞的前体,也是其物理通道。胶质管细胞与迁移神经母细胞之间的双向信号已被证明可调节前体细胞的增殖速率和新生成神经母细胞的迁移速率。我们发现埃兹蛋白和β-连环蛋白都存在于胶质管细胞的细胞膜上,这表明这些蛋白可能参与了那些信号传导过程。