Astrotactin provides a receptor system for CNS neuronal migration.
Astrotactin provides a receptor system for CNS neuronal migration.
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作者：
G. Fishell;M. Hatten
中枢神经系统神经元迁移是细胞运动的一种特殊形式，它阐述了大脑皮层区域的层状结构。为了定义神经胶质引导的神经元迁移中的神经元受体系统，开发了用于小鼠小脑颗粒神经元的体外测定，其提供了数百个迁移神经元的同时跟踪。分析了三种一般类型的受体系统，神经元-神经胶质细胞粘附配体astrotactin，IgG超家族的神经细胞粘附分子，N-CAM，L1和TAG-1，以及整联蛋白家族的β 1亚基。在没有免疫活性的情况下，迁移的小脑颗粒神经元的平均体外迁移率为12 μ m h-1，单个神经元的迁移率在0至70 μ m h-1之间。抗astrotactin抗体（或Fab）的加入显著降低了61%的平均神经元迁移率，导致80%的神经元迁移率低于8微米h-1。相比之下，单独或联合使用针对L1、N-CAM、TAG-1或β 1整联蛋白的阻断抗体（或Fab）不会降低神经元迁移的速率。通过视频增强对比微分干涉对比显微镜，抗astrotactin抗体的作用被认为是快速的。在15分钟的抗体应用，流到领先的过程中的细胞质细胞器停止，核从尾部转移到中央的位置，丝状伪足和片状伪足沿着领先的过程停止延伸。相关的视频和电子显微镜表明，由antiastrotactin抗体的逮捕机制涉及未能形成新的粘附位点沿着领先的过程和细胞骨架成分的解体。这些结果表明，astrotactin作为一个神经元受体颗粒神经元迁移沿着星形胶质纤维。
CNS neuronal migration is a specialized form of cell motility that sets forth the laminar structure of cortical regions of brain. To define the neuronal receptor systems in glial-guided neuronal migration, an in vitro assay was developed for mouse cerebellar granule neurons, which provides simultaneous tracking of hundreds of migrating neurons. Three general classes of receptor systems were analyzed, the neuron-glial adhesion ligand astrotactin, the neural cell adhesion molecules of the IgG superfamily, N-CAM, L1 and TAG-1, and the beta 1 subunit of the integrin family. In the absence of immune activities, migrating cerebellar granule neurons had an average in vitro migration rate of 12 microns h-1, with individual neurons exhibiting migration rates over a range between 0 to 70 microns h-1. The addition of anti-astrotactin antibodies (or Fabs) significantly reduced the mean rate of neuronal migration by sixty-one percent, resulting in eighty percent of the neurons having migration rates below 8 microns h-1. By contrast, blocking antibodies (or Fabs) against L1, N-CAM, TAG-1 or beta 1 integrin, individually or in combination, did not reduce the rate of neuronal migration. By video-enhanced contrast differential interference contrast microscopy the effects of anti-astrotactin antibodies were seen to be rapid. Within fifteen minutes of antibody application, streaming of cytoplasmic organelles into the leading process arrested, the nucleus shifted from a caudal to a central position, and the extension of filopodia and lamellopodia along the leading process ceased. Correlated video and electron microscopy suggested that the mechanism of arrest by antiastrotactin antibodies involved the failure to form new adhesion sites along the leading process and the disorganization of cytoskeletal components. These results suggest astrotactin acts as a neuronal receptor for granule neuron migration along astroglial fibers.