High-throughput kinase inhibitor screening reveals roles for Aurora and Nuak kinases in neurite initiation and dendritic branching.
High-throughput kinase inhibitor screening reveals roles for Aurora and Nuak kinases in neurite initiation and dendritic branching.
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DOI：
10.1038/s41598-021-87521-3
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发表时间：
2021-04-14
影响因子：
4.6
通讯作者：
Toyo-Oka K
中科院分区：
文献类型：
--
作者：
Blazejewski SM;Bennison SA;Liu X;Toyo-Oka K
激酶是多种细胞信号传导过程的重要调节剂，包括神经突形成-神经发育的基础步骤。异常轴突发芽和受损轴突再生失败与创伤性损伤、神经退行性疾病和癫痫发作等病症相关。研究神经突形成的机制将有助于确定潜在的治疗方法。我们使用激酶抑制剂库筛选了493种激酶抑制剂，并观察到45%影响Neuro 2a（N-2a）细胞的轴突发生。基于筛选，我们进一步研究了极光激酶A、B和C以及Nuak激酶1和2的作用。Aurora和Nuak激酶在神经系统中的作用尚未得到彻底研究。抑制或过度表达原代皮层神经元中的Aurora和Nuak激酶导致各种神经形态学缺陷，Aurora A调节神经突起始，Aurora B和C调节神经突起始和延伸，所有Aurora激酶调节树枝化，所有Nuak激酶调节神经突起始和延伸以及树枝化。我们对Aurora和Nuak激酶的高通量筛选和分析揭示了它们的功能，并可能有助于鉴定治疗剂。
Kinases are essential regulators of a variety of cellular signaling processes, including neurite formation—a foundational step in neurodevelopment. Aberrant axonal sprouting and failed regeneration of injured axons are associated with conditions like traumatic injury, neurodegenerative disease, and seizures. Investigating the mechanisms underlying neurite formation will allow for identification of potential therapeutics. We used a kinase inhibitor library to screen 493 kinase inhibitors and observed that 45% impacted neuritogenesis in Neuro2a (N-2a) cells. Based on the screening, we further investigated the roles of Aurora kinases A, B, and C and Nuak kinases 1 and 2. The roles of Aurora and Nuak kinases have not been thoroughly studied in the nervous system. Inhibition or overexpression of Aurora and Nuak kinases in primary cortical neurons resulted in various neuromorphological defects, with Aurora A regulating neurite initiation, Aurora B and C regulating neurite initiation and elongation, all Aurora kinases regulating arborization, and all Nuak kinases regulating neurite initiation and elongation and arborization. Our high-throughput screening and analysis of Aurora and Nuak kinases revealed their functions and may contribute to the identification of therapeutics.
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影响因子：
6.9
作者：
Chen, Dongdong;Yu, Shan Ping;Wei, Ling
通讯作者：
Wei, Ling
DOI：
10.1042/bj20131152
发表时间：
2014-01-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Banerjee S;Buhrlage SJ;Huang HT;Deng X;Zhou W;Wang J;Traynor R;Prescott AR;Alessi DR;Gray NS
通讯作者：
Gray NS
DOI：
10.1016/0736-5748(93)90007-z
发表时间：
1993-06-01
影响因子：
1.8
作者：
CABELL, L;AUDESIRK, G
通讯作者：
AUDESIRK, G
影响因子：
4.1
作者：
Anderson, Kelly;Lai, Zhihong;Yang, Jingsong
通讯作者：
Yang, Jingsong
影响因子：
8
作者：
Gwee, Serene S. L.;Radford, Rowan A. W.;Chung, Roger S.
通讯作者：
Chung, Roger S.