Mouse Biology Unit, European Molecular Biology Laboratory, Monterotondo, Rome, Italy.
Mol Cell Biol. 2013 Mar;33(6):1114-23. doi: 10.1128/MCB.01044-12. Epub 2012 Dec 28.
Acetylation of α-tubulin at lysine 40 (K40) is a well-conserved posttranslational modification that marks long-lived microtubules but has poorly understood functional significance. Recently, αTAT1, a member of the Gcn5-related N-acetyltransferase superfamily, has been identified as an α-tubulin acetyltransferase in ciliated organisms. Here, we explored the function of αTAT1 with the aim of understanding the consequences of αTAT1-mediated microtubule acetylation. We demonstrate that α-tubulin is the major target of αTAT1 but that αTAT1 also acetylates itself in a regulatory mechanism that is required for effective modification of tubulin. We further show that in mammalian cells, αTAT1 promotes microtubule destabilization and accelerates microtubule dynamics. Intriguingly, this effect persists in an αTAT1 mutant with no acetyltransferase activity, suggesting that interaction of αTAT1 with microtubules, rather than acetylation per se, is the critical factor regulating microtubule stability. Our data demonstrate that αTAT1 has cellular functions that extend beyond its classical enzymatic activity as an α-tubulin acetyltransferase.
α-微管蛋白赖氨酸 40 位乙酰化（K40）是一种广泛存在的翻译后修饰，它标记长寿命的微管，但功能意义尚未完全清楚。最近，Gcn5 相关 N-乙酰转移酶超家族的成员αTAT1 已被鉴定为纤毛生物中的一种α-微管蛋白乙酰转移酶。在这里，我们研究了αTAT1 的功能，旨在了解由αTAT1 介导的微管乙酰化的后果。我们证明α-微管蛋白是αTAT1 的主要靶标，但αTAT1 也通过一种调节机制自身乙酰化，这种调节机制是有效修饰微管所必需的。我们进一步表明，在哺乳动物细胞中，αTAT1 促进微管解稳定化并加速微管动力学。有趣的是，这种效应在没有乙酰转移酶活性的αTAT1 突变体中仍然存在，这表明αTAT1 与微管的相互作用，而不是乙酰化本身，是调节微管稳定性的关键因素。我们的数据表明，αTAT1 具有超越其作为经典α-微管蛋白乙酰转移酶的细胞功能。
