Myosin X regulates neuronal radial migration through interacting with N-cadherin.
Myosin X regulates neuronal radial migration through interacting with N-cadherin.
复制标题
肌球蛋白 X 通过与 N-钙粘蛋白相互作用来调节神经元径向迁移。
DOI：
10.3389/fncel.2015.00326
复制
发表时间：
2015
影响因子：
5.3
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Lai M;Guo Y;Ma J;Yu H;Zhao D;Fan W;Ju X;Sheikh MA;Malik YS;Xiong W;Guo W;Zhu X
正常的脑功能取决于发育过程中神经元的迁移，而神经元的迁移受细胞骨架动力学和细胞-细胞粘附的调节。肌球蛋白X（Myo 10）是肌球蛋白家族的一个非特征性成员，是在许多不同细胞环境中调节细胞运动的细胞骨架的重要调节因子。我们以前报道过Myo 10是发育中的大脑皮层神经元迁移所必需的，但其潜在机制仍然很大程度上未知。在这里，我们发现，敲低Myo 10表达干扰迁移神经元的径向胶质纤维的粘附，通过废除表面神经元钙粘蛋白（N-cadherin）的表达，从而损害神经元的迁移在发育皮层。接着，我们发现Myo 10通过其FERM结构域与N-cadherin细胞结构域相互作用。此外，我们发现Myo 10的敲除破坏了N-cadherin的亚细胞分布，并导致N-cadherin定位于高尔基体和内体分选囊泡。总之，这些结果揭示了Myo 10与N-cadherin相互作用并调节其细胞表面表达的新机制，这是神经元粘附和迁移所必需的。
Proper brain function depends on correct neuronal migration during development, which is known to be regulated by cytoskeletal dynamics and cell-cell adhesion. Myosin X (Myo10), an uncharacteristic member of the myosin family, is an important regulator of cytoskeleton that modulates cell motilities in many different cellular contexts. We previously reported that Myo10 was required for neuronal migration in the developing cerebral cortex, but the underlying mechanism was still largely unknown. Here, we found that knockdown of Myo10 expression disturbed the adherence of migrating neurons to radial glial fibers through abolishing surface Neuronal cadherin (N-cadherin) expression, thereby impaired neuronal migration in the developmental cortex. Next, we found Myo10 interacted with N-cadherin cellular domain through its FERM domain. Furthermore, we found knockdown of Myo10 disrupted N-cadherin subcellular distribution and led to localization of N-cadherin into Golgi apparatus and endosomal sorting vesicle. Taking together, these results reveal a novel mechanism of Myo10 interacting with N-cadherin and regulating its cell-surface expression, which is required for neuronal adhesion and migration.