SCG10, a microtubule destabilizing factor, stimulates the neurite outgrowth by modulating microtubule dynamics in rat hippocampal primary cultured neurons
SCG10, a microtubule destabilizing factor, stimulates the neurite outgrowth by modulating microtubule dynamics in rat hippocampal primary cultured neurons
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DOI：
10.1002/neu.20295
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发表时间：
2006-09-01
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影响因子：
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通讯作者：
Mori, Nozomu
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文献类型：
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作者：
Morii, Hiroshi;Shiraishi-Yamaguchi, Yoko;Mori, Nozomu
微管动力学是神经突起生长的关键因素之一，它受多种调节因子的调节，决定神经生长锥的行为，并形成专门的神经元形状。SCG10是一种神经元特异性stathmin蛋白，具有有效的微管不稳定因子，并富集在发育神经元的生长锥中。我们使用大鼠海马原代培养神经元研究了SCG10在神经突起生长中的功能作用。使用短干扰RNA双链体对SCG10进行遗传操作显著降低了SCG10的表达水平，并显著抑制了神经突的生长。免疫耗竭实验证实了这一结果。另一方面，使用聚精氨酸标签的SCG10的蛋白转导刺激神经突生长。SCG10表达水平的这种操纵影响生长锥内的微管形态。SCG10水平的降低将形态转化为更稳定的状态，而增加将形态转化为更动态的状态。然而，过量的SCG10诱导神经突收缩由于过量的微管解体。这些结果表明，SCG 10作为一个重要的调节因子的生长锥运动，通过增强微管动力学，可能通过增加灾难的频率。(c)2006 Wiley Periodicals，Inc.
Microtubule dynamics, one of the key elements in neurite outgrowth, is regulated by various regulatory factors to determine the behavior of the neuronal growth cone and to form the specialized neuronal shape. SCG10 is a neuron-specific stathmin protein with a potent microtubule destabilizing factor and is enriched in the growth cones of the developing neurons. We investigated the functional role of SCG10 in neurite outgrowth using rat hippocampal primary cultured neurons. Genetic manipulation of SCG10 using a short-interfering RNA duplex markedly decreased the SCG10 expression level and significantly suppressed neurite outgrowth. This result was confirmed by immunodepletion experiments. On the other hand, the protein transduction of SCG10 using a polyarginine tag stimulated neurite outgrowth. Such manipulation of the SCG10 expression level affected microtubule morphology within the growth cones. A decrease in the SCG10 level converted the morphology to a more stable state, while an increase converted the morphology to a more dynamic state. However, an excess of SCG10 induced neurite retraction due to an excess of microtubule disassembly. These results suggest that SCG10 serves as an important regulatory factor of growth cone motility by enhancing microtubule dynamics, possibly through increasing the catastrophe frequency. (c) 2006 Wiley Periodicals, Inc.