Involvement of Filamin A and Filamin A-interacting protein (FILIP) in controlling the start and cell shape of radially migrating cortical neurons
Involvement of Filamin A and Filamin A-interacting protein (FILIP) in controlling the start and cell shape of radially migrating cortical neurons
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DOI：
10.1111/j.1447-073x.2005.00101.x
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发表时间：
2005-03
影响因子：
1.2
通讯作者：
Makoto Sato;T. Nagano
中科院分区：
文献类型：
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作者：
Makoto Sato;T. Nagano
精确调控的放射状细胞迁移出脑室区对于皮质生成是必不可少的。然而，控制迁移开始和迁移细胞形状的动力学的分子机制仍然难以捉摸。在这里，我们展示了新的机制，可以系绳心室区细胞和控制迁移细胞的形状。Filamin A相互作用蛋白（FILIP）是一种新型蛋白质，它与细胞运动所必需的肌动蛋白结合蛋白Filamin A相互作用，并诱导其在COS-7细胞中降解。细丝蛋白A的降解在FILIP mRNA定位的皮质心室区中指示。此外，大多数过度表达FILIP的心室区细胞在外植体中不能迁移。这些结果表明，FILIP通过细丝蛋白A-F-肌动蛋白轴来控制新皮层细胞从心室区迁移的开始。细丝蛋白A还决定迁移的新皮层神经元的形状，这些神经元在迁移过程中表现出全局形态学变化和复杂的行为。由突变体细丝蛋白A表达引起的细丝蛋白A功能障碍阻止细胞获得朝向特定方向的一致极性，并降低心室下区和中间区的运动性。相反，Filamin A过表达，实现了一个短的干扰RNA的FILIP，促进发展和维护的双极形状也在脑室下和中间区。这些结果表明，细丝蛋白A的量有助于迁移神经元确定他们的迁移模式，多极或双极，进入皮质板之前，FILIP负责，至少部分，细丝蛋白A的内容迁移神经元。
Precisely regulated radial cell migration out of the ventricular zone is essential for corticogenesis. However, molecular mechanisms controlling the start of migration and the dynamics of migrating cell shape remain elusive. Here, we show novel mechanisms that can tether ventricular zone cells and control migrating cell shape. The novel protein Filamin A-interacting protein (FILIP) interacts with Filamin A, an indispensable actin-binding protein for cell motility, and induces its degradation in COS-7 cells. Degradation of Filamin A is indicated in the cortical ventricular zone where FILIP mRNA localizes. Furthermore, most ventricular zone cells that overexpress FILIP fail to migrate in explants. These results indicate that FILIP acts through a Filamin A-F-actin axis to control the start of neocortical cell migration from the ventricular zone. Filamin A also determines the shape of migrating neocortical neurons, which show global morphological changes and complicated behavior during that migration. Dysfunction of Filamin A, caused by a mutant Filamin A expression, prevents cells from acquiring consistent polarity toward specific direction and decreases motility in the subventricular and intermediate zones. In contrast, Filamin A overexpression, achieved by a short interfering RNA for FILIP, promotes the development and maintenance of a bipolar shape also in the subventricular and intermediate zones. These results suggest that the amount of Filamin A helps migrating neurons determine their mode of migration, multipolar or bipolar, prior to entering the cortical plate and that FILIP is responsible, at least in part, for the Filamin A content of migrating neurons.