Institut Curie, PSL Research University, CNRS UMR3348, Orsay, France.
Université Paris-Saclay, CNRS UMR3348, Orsay, France.
Nat Rev Mol Cell Biol. 2020 Jun;21(6):307-326. doi: 10.1038/s41580-020-0214-3. Epub 2020 Feb 27.
Microtubules are core components of the eukaryotic cytoskeleton with essential roles in cell division, shaping, motility and intracellular transport. Despite their functional heterogeneity, microtubules have a highly conserved structure made from almost identical molecular building blocks: the tubulin proteins. Alternative tubulin isotypes and a variety of post-translational modifications control the properties and functions of the microtubule cytoskeleton, a concept known as the 'tubulin code'. Here we review the current understanding of the molecular components of the tubulin code and how they impact microtubule properties and functions. We discuss how tubulin isotypes and post-translational modifications control microtubule behaviour at the molecular level and how this translates into physiological functions at the cellular and organism levels. We then go on to show how fine-tuning of microtubule function by some tubulin modifications can affect homeostasis and how perturbation of this fine-tuning can lead to a range of dysfunctions, many of which are linked to human disease.
微管是真核细胞骨架的核心组成部分，在细胞分裂、形态发生、运动和细胞内运输中具有重要作用。尽管它们具有功能异质性，但微管具有高度保守的结构，由几乎相同的分子构建块组成：微管蛋白。替代的微管蛋白同工型和多种翻译后修饰控制微管细胞骨架的特性和功能，这一概念被称为“微管蛋白密码”。在这里，我们回顾了微管蛋白密码的分子成分的现有理解，以及它们如何影响微管的特性和功能。我们讨论了微管蛋白同工型和翻译后修饰如何在分子水平上控制微管的行为，以及这如何转化为细胞和生物体水平的生理功能。然后，我们展示了一些微管蛋白修饰如何通过微调微管功能来影响内稳态，以及这种微调的干扰如何导致一系列功能障碍，其中许多与人类疾病有关。
