Lu Yu-Ming
Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.
School of Biological Sciences, The University of Hong Kong, Hong Kong SAR, China.
J Cell Sci. 2025 Jul 15;138(14). doi: 10.1242/jcs.263431.
Acetylation of α-tubulin at lysine 40 (K40) has been studied in many model organisms for decades, mainly by manipulating levels of deacetylase and acetyltransferase enzymes, such as the α-tubulin acetyltransferase MEC-17 (also known as ATAT1). Observations that acetylation accumulates in some long-lived microtubules and that MEC-17 is important for maintaining microtubule organization and key cellular functions have led to the prevailing view that K40 acetylation stabilizes and protects microtubules, although many questions about its precise function remain. Recent gene editing of endogenous α-tubulin and in vitro microtubule polymerization assays have indicated that K40 acetylation itself does not maintain microtubule structure as MEC-17 does, but rather negatively regulates specific aspects of microtubule dynamics (i.e. nucleation and shrinkage but not elongation) and slightly impairs neuronal extension. This Opinion article discusses multiple important studies on α-tubulin K40 acetylation that have shaped our understanding of its function since its discovery in the 1980s, with the aim of clarifying the actual role of this major tubulin post-translational modification.
几十年来，人们在许多模式生物中研究了赖氨酸40（K40）位点α-微管蛋白的乙酰化，主要是通过调控去乙酰化酶和乙酰转移酶的水平，比如α-微管蛋白乙酰转移酶MEC-17（也称为ATAT1）。有观察发现，乙酰化在一些长寿微管中积累，且MEC-17对维持微管组织和关键细胞功能很重要，这导致了一种普遍观点，即K40乙酰化能稳定和保护微管，尽管关于其确切功能仍有许多问题。最近对内源性α-微管蛋白的基因编辑和体外微管聚合试验表明，K40乙酰化本身并不像MEC-17那样维持微管结构，而是对微管动力学的特定方面（即成核和收缩而非伸长）起负调控作用，并轻微损害神经元延伸。这篇观点文章讨论了自20世纪80年代发现α-微管蛋白K40乙酰化以来，多项关于它的重要研究，这些研究塑造了我们对其功能的理解，目的是阐明这种主要微管蛋白翻译后修饰的实际作用。
