Mouse Biology Unit, EMBL, Via Ramarini 32, Monterotondo 00015, Italy.
Nat Commun. 2013;4:1962. doi: 10.1038/ncomms2962.
Post-translational modification of tubulin serves as a powerful means for rapidly adjusting the functional diversity of microtubules. Acetylation of the ε-amino group of K40 in α-tubulin is one such modification that is highly conserved in ciliated organisms. Recently, αTAT1, a Gcn5-related N-acetyltransferase, was identified as an α-tubulin acetyltransferase in Tetrahymena and C. elegans. Here we generate mice with a targeted deletion of Atat1 to determine its function in mammals. Remarkably, we observe a loss of detectable K40 α-tubulin acetylation in these mice across multiple tissues and in cellular structures such as cilia and axons where acetylation is normally enriched. Mice are viable and develop normally, however, the absence of Atat1 impacts upon sperm motility and male mouse fertility, and increases microtubule stability. Thus, αTAT1 has a conserved function as the major α-tubulin acetyltransferase in ciliated organisms and has an important role in regulating subcellular specialization of subsets of microtubules.
翻译后修饰的微管蛋白作为一种快速调节微管功能多样性的有效手段。乙酰化 K40 的 ε-氨基在α-微管蛋白中是一种在纤毛生物中高度保守的修饰。最近，Gcn5 相关的 N-乙酰转移酶αTAT1 被鉴定为四膜虫和秀丽隐杆线虫中的α-微管蛋白乙酰转移酶。在这里，我们生成了靶向敲除 Atat1 的小鼠，以确定其在哺乳动物中的功能。值得注意的是，我们观察到这些小鼠的多种组织以及纤毛和轴突等通常富含乙酰化的细胞结构中，可检测到的 K40α-微管蛋白乙酰化的缺失。然而，这些小鼠是有活力且正常发育的，只是 Atat1 的缺失会影响精子的运动能力和雄性小鼠的生育能力，并增加微管的稳定性。因此，αTAT1 作为纤毛生物中主要的α-微管蛋白乙酰转移酶具有保守的功能，在调节微管亚细胞特化方面具有重要作用。
