Leading Tip Drives Soma Translocation via Forward F-Actin Flow during Neuronal Migration
Leading Tip Drives Soma Translocation via Forward F-Actin Flow during Neuronal Migration
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DOI：
10.1523/jneurosci.0240-10.2010
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发表时间：
2010-08-11
影响因子：
5.3
通讯作者：
Yuan, Xiao-bing
中科院分区：
文献类型：
--
作者：
He, Min;Zhang, Zheng-hong;Yuan, Xiao-bing
神经元迁移涉及胞体前导突起和胞体移位的协调延伸，但不同亚细胞区，包括前导突起和细胞后部，在胞体移位中的相对贡献尚不清楚。通过对培养神经元受限区域细胞骨架成分的局部操作，我们研究了神经元迁移过程中产生胞体移位牵引力的分子机制。在培养的活跃迁移的小脑颗粒细胞中，顶端的生长锥(GC)样结构表现出高度的动力学，切断顶端或破坏其动力学在几分钟内抑制了胞体的移位。胞体转位也被沿前导突起的F-肌动蛋白的局部破坏所抑制，但在胞体不被局部破坏，而沿前导突起或胞体的微管的破坏加速了胞体的转位。使用GFP-α-肌动蛋白的荧光散斑显微镜显示，F-肌动蛋白沿前导过程与SOMA转位相关，并且是SOMA转位所必需的，这种F-肌动蛋白流动依赖于肌球蛋白II的活性。在迁移神经元中，肌球蛋白II活性在前端较高，而在胞体较低，增大或减小这种前后差异可加速或阻碍胞体的前进。因此，在神经元迁移过程中，引导过程的尖端通过肌球蛋白II依赖的前向F-肌动蛋白流动，沿着引导过程积极地将胞体向前拉。
Neuronal migration involves coordinated extension of the leading process and translocation of the soma, but the relative contribution of different subcellular regions, including the leading process and cell rear, in driving soma translocation remains unclear. By local manipulation of cytoskeletal components in restricted regions of cultured neurons, we examined the molecular machinery underlying the generation of traction force for soma translocation during neuronal migration. In actively migrating cerebellar granule cells in culture, a growth cone (GC)-like structure at the leading tip exhibits high dynamics, and severing the tip or disrupting its dynamics suppressed soma translocation within minutes. Soma translocation was also suppressed by local disruption of F-actin along the leading process but not at the soma, whereas disrupting microtubules along the leading process or at the soma accelerated soma translocation. Fluorescent speckle microscopy using GFP-alpha-actinin showed that a forward F-actin flow along the leading process correlated with and was required for soma translocation, and such F-actin flow depended on myosin II activity. In migrating neurons, myosin II activity was high at the leading tip but low at the soma, and increasing or decreasing this front-to-rear difference accelerated or impeded soma advance. Thus, the tip of the leading process actively pulls the soma forward during neuronal migration through a myosin II-dependent forward F-actin flow along the leading process.