Aurora kinase B regulates axonal outgrowth and regeneration in the spinal motor neurons of developing zebrafish
Aurora kinase B regulates axonal outgrowth and regeneration in the spinal motor neurons of developing zebrafish
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DOI：
10.1007/s00018-018-2780-5
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发表时间：
2018-12-01
影响因子：
8
通讯作者：
Chung, Roger S.
中科院分区：
文献类型：
--
作者：
Gwee, Serene S. L.;Radford, Rowan A. W.;Chung, Roger S.
极光蛋白B(Aurora Kinase B，AurkB)是一种丝氨酸/苏氨酸蛋白激酶，在细胞分裂和胞质分裂中具有重要的作用，在健康的增殖细胞和癌细胞中有显著的表达。然而，AurkB在分化和非分裂细胞中的作用还没有得到广泛的研究。此前，我们已经描述了实验性轴突横断后培养的皮质神经元中AurkB表达的显著上调。这有点令人惊讶，因为AurkB的表达通常只与细胞分裂有关，Frangini等人。(Mol Cell 51：647-661,2013)；Hegarat等人。(J Cell Biol 195：1103-1113,2011)；Lu等人。(生物化学杂志283：31785-31790,2008年)；特拉卡拉等人。(细胞周期12：1030-1041,2014)。在此，我们首次描述了AurkB在终末分化神经元中的作用。AurkB主要表达于斑马鱼大脑和脊髓的有丝分裂后神经元。AurkB在斑马鱼脊髓运动神经元发育过程中的表达发生变化。使用药物和遗传操作来削弱AurkB的活性导致截断和异常的运动轴突形态，而AurkB的过度表达导致轴突延长。进一步的药物抑制再生轴突的AurkB活性延缓了UV激光损伤后轴突的恢复。总而言之，这些结果表明AurkB在调节神经元发育和轴突生长方面发挥了迄今未见报道的作用。
Aurora kinase B (AurkB) is a serine/threonine protein kinase with a well-characterised role in orchestrating cell division and cytokinesis, and is prominently expressed in healthy proliferating and cancerous cells. However, the role of AurkB in differentiated and non-dividing cells has not been extensively explored. Previously, we have described a significant upregulation of AurkB expression in cultured cortical neurons following an experimental axonal transection. This is somewhat surprising, as AurkB expression is generally associated only with dividing cells Frangini et al. (Mol Cell 51:647-661, 2013); Hegarat et al. (J Cell Biol 195:1103-1113, 2011); Lu et al. (J Biol Chem 283:31785-31790, 2008); Trakala et al. (Cell Cycle 12:1030-1041, 2014). Herein, we present the first description of a role for AurkB in terminally differentiated neurons. AurkB was prominently expressed within post-mitotic neurons of the zebrafish brain and spinal cord. The expression of AurkB varied during the development of the zebrafish spinal motor neurons. Utilising pharmacological and genetic manipulation to impair AurkB activity resulted in truncation and aberrant motor axon morphology, while overexpression of AurkB resulted in extended axonal outgrowth. Further pharmacological inhibition of AurkB activity in regenerating axons delayed their recovery following UV laser-mediated injury. Collectively, these results suggest a hitherto unreported role of AurkB in regulating neuronal development and axonal outgrowth.