Ran-dependent TPX2 activation promotes acentrosomal microtubule nucleation in neurons
Ran-dependent TPX2 activation promotes acentrosomal microtubule nucleation in neurons
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DOI：
10.1038/srep42297
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发表时间：
2017-02-13
影响因子：
4.6
通讯作者：
Hwang, Eric
中科院分区：
文献类型：
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作者：
Chen, Wen-Shin;Chen, Yi-Ju;Hwang, Eric
微管（MT）细胞骨架是必要的形成形态适当的神经元。无核体MT组织中心的存在已被提出，但其身份仍然难以捉摸。在这里，我们提供的证据表明TPX2是这个无丝胞体MT组织中心的重要组成部分。首先，在tpx2缺失的神经元中，神经突伸长受到损害。此外，TPX2定位于中心体和与MT结合的神经突轴。TPX2的消耗降低了神经突尖端和基部的MT形成频率，这与活性gtp结合的Ran蛋白富集的区域精确相关。此外，过表达Ran的下游效应物，进口，损害MT的形成和神经元的形态发生。最后，应用一种转录输入蛋白信号干扰化合物，观察TPX2耗竭对MT动力学的影响。总之，这些数据提示了一个模型，在该模型中，依赖于ran的TPX2激活促进了神经元中无丝胞体MT成核。
The microtubule (MT) cytoskeleton is essential for the formation of morphologically appropriate neurons. The existence of the acentrosomal MT organizing center in neurons has been proposed but its identity remained elusive. Here we provide evidence showing that TPX2 is an important component of this acentrosomal MT organizing center. First, neurite elongation is compromised in TPX2-depleted neurons. In addition, TPX2 localizes to the centrosome and along the neurite shaft bound to MTs. Depleting TPX2 decreases MT formation frequency specifically at the tip and the base of the neurite, and these correlate precisely with the regions where active GTP-bound Ran proteins are enriched. Furthermore, overexpressing the downstream effector of Ran, importin, compromises MT formation and neuronal morphogenesis. Finally, applying a Ran-importin signaling interfering compound phenocopies the effect of TPX2 depletion on MT dynamics. Together, these data suggest a model in which Ran-dependent TPX2 activation promotes acentrosomal MT nucleation in neurons.