Filopodia are required for cortical neurite initiation
Filopodia are required for cortical neurite initiation
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DOI：
10.1038/ncb1654
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发表时间：
2007-12-01
影响因子：
21.3
通讯作者：
Gertler, Frank B.
中科院分区：
文献类型：
--
作者：
Dent, Erik W.;Kwiatkowski, Adam V.;Gertler, Frank B.
神经突起从细胞体延伸出来是形成功能神经系统所必需的；然而，神经发生的潜在机制却知之甚少。Ena/Vasp蛋白调节肌动蛋白的动态，并调节细胞突起的精加工。我们最近报道，在Ena/Vasp缺失的小鼠中，皮质轴索的形成丢失，并且Ena/Vasp缺失的皮质神经元缺乏丝状足基，无法详细阐述轴突。在这里，我们报告，通过异位表达肌动蛋白核蛋白mDia2来恢复丝状足突的形成，可以挽救Ena/Vasp缺失神经元的神经发生。相反，阻止丝状足突形成的野生型神经元不能精细地突起。我们还报告了层粘连蛋白，它促进丝状足状肌动蛋白丰富的突起的形成，拯救了Ena/Vasp缺陷神经元的神经发生。因此，丝状伪足的形成是大脑皮层神经元发生的关键前提。轴突的起始也需要微管延伸到丝状伪足中，这表明肌动蛋白-细丝束和丝状伪足内动态微管之间的相互作用对神经元的发生至关重要。
Extension of neurites from a cell body is essential to form a functional nervous system; however, the mechanisms underlying neuritogenesis are poorly understood. Ena/VASP proteins regulate actin dynamics and modulate elaboration of cellular protrusions. We recently reported that cortical axon-tract formation is lost in Ena/VASP-null mice and Ena/VASP-null cortical neurons lack filopodia and fail to elaborate neurites. Here, we report that neuritogenesis in Ena/VASP-null neurons can be rescued by restoring filopodia formation through ectopic expression of the actin nucleating protein mDia2. Conversely, wildtype neurons in which filopodia formation is blocked fail to elaborate neurites. We also report that laminin, which promotes the formation of filopodia-like actin-rich protrusions, rescues neuritogenesis in Ena/VASP-deficient neurons. Therefore, filopodia formation is a key prerequisite for neuritogenesis in cortical neurons. Neurite initiation also requires microtubule extension into filopodia, suggesting that interactions between actin-filament bundles and dynamic microtubules within filopodia are crucial for neuritogenesis.