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NWD1 通过调节微管稳定性影响神经元轴突的延伸。

NWD1 influences the extension of neuronal axons by regulating microtubule stability.

机构信息

Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, Co-innovation Center of Neuroregeneration, Medical School, Nantong University, Nantong, Jiangsu Province, 226001, China.

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu Province, 226001, China.

出版信息

Biochem Biophys Res Commun. 2024 Nov 19;734:150775. doi: 10.1016/j.bbrc.2024.150775. Epub 2024 Oct 5.

Abstract

Proteins belonging to the STAND (signal transduction ATPases with numerous domains) family have been implicated in crucial functions across various signal transduction pathways, encompassing both apoptosis and innate immune responses. In this study, we have identified NWD1, a member of the STAND superfamily, as a gene that regulates neurite outgrowth. This was confirmed by siRNA knockdown assay in E18 neurons. A zebrafish model was utilized to create NWD1 knockdown using the NgAgo-gDNA system, revealing the significant role of NWD1 in neurogenesis. We further revealed that NWD1 siRNA reduced the acetylated tubulin protein, and changed the ratio of soluble and polymerized tubulin. Moreover, we investigated the mechanism underlying the regulation of NWD1-mediated microtubule dynamics, and MAP1B may be a target gene. This research unveiled, for the first time, the potential role of NWD1 in regulating axon outgrowth through modulating the ratio of acetylated tubulin.

摘要

属于 STAND(具有众多结构域的信号转导 ATP 酶)家族的蛋白质已被牵连到各种信号转导途径中的关键功能中,包括细胞凋亡和先天免疫反应。在这项研究中,我们发现 NWD1 是 STAND 超家族的一个成员,是调节神经突生长的基因。这一点通过 E18 神经元中的 siRNA 敲低实验得到了证实。我们利用 zebrafish 模型,使用 NgAgo-gDNA 系统敲低 NWD1,揭示了 NWD1 在神经发生中的重要作用。我们进一步揭示,NWD1 siRNA 降低了乙酰化微管蛋白的含量,并改变了微管蛋白的可溶性和聚合状态的比例。此外,我们研究了 NWD1 调节微管动力学的机制,MAP1B 可能是一个靶基因。这项研究首次揭示了 NWD1 通过调节乙酰化微管蛋白的比例来调节轴突生长的潜在作用。

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