Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg Gothenburg, Sweden.
Front Cell Neurosci. 2013 Sep 24;7:161. doi: 10.3389/fncel.2013.00161. eCollection 2013.
Neuronal progenitors capable of long distance migration are produced throughout life in the subventricular zone (SVZ). Migration from the SVZ is carried out along a well-defined pathway called the rostral migratory stream (RMS). Our recent finding of the specific expression of the cytoskeleton linker protein radixin in neuroblasts suggests a functional role for radixin in RMS migration. The ezrin-radixin-moesin (ERM) family of proteins is capable of regulating migration through interaction with the actin cytoskeleton and transmembrane proteins. The ERM proteins are differentially expressed in the RMS with radixin and moesin localized to neuroblasts, and ezrin expression confined to astrocytes of the glial tubes. Here, we inhibited radixin function using the quinocarmycin analog DX52-1 which resulted in reduced neuroblast migration in vitro, while glial migration remained unaltered. Furthermore, the morphology of neuroblasts was distorted resulting in a rounded shape with no or short polysialylated neural cell adhesion molecule positive processes. Intracerebroventricular infusion of the radixin inhibitor resulted in accumulation of neuroblasts in the anterior SVZ. Neuroblast chains were short and intermittently interrupted in the SVZ and considerably disorganized in the RMS. Moreover, we studied the proliferation activity in the RMS after radixin inhibition, since concentrated radixin expression has been demonstrated in the cleavage furrow of dividing cells, which indicates a role of radixin in cell division. Radixin inhibition decreased neuroblast proliferation, whereas the proliferation of other cells in the RMS was not affected. Our results demonstrate a significant role for radixin in neuroblast proliferation and migration.
神经祖细胞能够在整个生命过程中在侧脑室下区（SVZ）产生长距离迁移。从 SVZ 的迁移是沿着一个称为前迁移流（RMS）的明确途径进行的。我们最近发现细胞骨架连接蛋白 radixin 在神经母细胞中的特异性表达表明 radixin 在 RMS 迁移中具有功能作用。ezrin-radixin-moesin（ERM）蛋白家族能够通过与肌动蛋白细胞骨架和跨膜蛋白相互作用来调节迁移。ERM 蛋白在 RMS 中表达不同，radixin 和 moesin 定位于神经母细胞，而 ezrin 表达局限于神经胶质管中的星形胶质细胞。在这里，我们使用 quinocarmycin 类似物 DX52-1 抑制 radixin 功能，导致体外神经母细胞迁移减少，而神经胶质细胞迁移保持不变。此外，神经母细胞的形态被扭曲，导致圆形，没有或短的多涎酸化神经细胞粘附分子阳性过程。脑室腔内输注 radixin 抑制剂导致神经母细胞在前 SVZ 中积累。神经母细胞链在 SVZ 中短而间歇性中断，在 RMS 中严重混乱。此外，我们研究了 radixin 抑制后 RMS 中的增殖活性，因为已经在分裂细胞的分裂沟中证明了浓缩的 radixin 表达，这表明 radixin 在细胞分裂中具有作用。radixin 抑制减少了神经母细胞的增殖，而 RMS 中其他细胞的增殖不受影响。我们的结果表明 radixin 在神经母细胞增殖和迁移中具有重要作用。
