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微管乙酰化在细胞功能和疾病中的作用。

Role of tubulin acetylation in cellular functions and diseases.

机构信息

Department of Anatomy and Cell Biology, Teikyo University School of Medicine, 2-11-1 Kaga Itabashi-ku, Tokyo, 173-8605, Japan.

出版信息

Med Mol Morphol. 2020 Dec;53(4):191-197. doi: 10.1007/s00795-020-00260-8. Epub 2020 Jul 6.

DOI:10.1007/s00795-020-00260-8
PMID:32632910
Abstract

Acetylation is a well-studied post-translational modification (PTM) of tubulin. Acetylated tubulin is present in the centrioles, primary cilia, and flagella, which contain long-lived stable microtubules. Tubulin acetylation plays an important role in cellular activities including cell polarity, cell migration, vesicle transport, and cell development. Cryo-electron microscopy reconstructions have revealed conformational changes in acetylated tubulin, revealing a reduction in intermonomer interactions among tubulins and an increase in microtubule elasticity. The kinetics of conformational changes in acetylated tubulin may elucidate microtubule functions in these cellular activities. Abnormal tubulin acetylation has been implicated in neurodegenerative disorders, ciliopathies, and cancers. Thus, it is important to elucidate the mechanisms underlying tubulin acetylation and its effects on cellular activity to understand these diseases and to design potential therapeutic strategies. This review discusses the cellular distribution and dynamics of acetylated tubulin and its role in regulating cellular activities.

摘要

乙酰化是微管蛋白的一种研究得很好的翻译后修饰(PTM)。乙酰化的微管蛋白存在于中心体、初级纤毛和鞭毛中,这些结构包含长寿命的稳定微管。微管蛋白乙酰化在细胞活动中起着重要作用,包括细胞极性、细胞迁移、囊泡运输和细胞发育。低温电子显微镜重建揭示了乙酰化微管蛋白的构象变化,显示微管蛋白之间的相互作用减少,微管的弹性增加。乙酰化微管蛋白构象变化的动力学可能阐明微管在这些细胞活动中的功能。异常的微管蛋白乙酰化与神经退行性疾病、纤毛病和癌症有关。因此,阐明微管蛋白乙酰化的机制及其对细胞活动的影响对于理解这些疾病和设计潜在的治疗策略非常重要。这篇综述讨论了乙酰化微管蛋白的细胞分布和动力学及其在调节细胞活动中的作用。

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