αTAT1 is the major α-tubulin acetyltransferase in mice
αTAT1 is the major α-tubulin acetyltransferase in mice
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DOI：
10.1038/ncomms2962
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发表时间：
2013-06-01
影响因子：
16.6
通讯作者：
Heppenstall, Paul A.
中科院分区：
文献类型：
--
作者：
Kalebic, Nereo;Sorrentino, Simona;Heppenstall, Paul A.
微管蛋白的翻译后修饰是快速调节微管功能多样性的有力手段。α-微管蛋白中K40的ε-氨基的乙酰化是一种在纤毛生物中高度保守的修饰。最近，在四膜虫和C.优美的在这里，我们产生了一个有针对性的删除Atat 1的小鼠，以确定其在哺乳动物中的功能。值得注意的是，我们在这些小鼠的多个组织和细胞结构中观察到可检测的K40 α-微管蛋白乙酰化的损失，如纤毛和轴突，其中乙酰化通常是富集的。小鼠存活并正常发育，然而，Atat 1的缺乏会影响精子活力和雄性小鼠生育力，并增加微管稳定性。因此，α TAT 1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，并且在调节微管亚群的亚细胞特化中具有重要作用。
Post-translational modification of tubulin serves as a powerful means for rapidly adjusting the functional diversity of microtubules. Acetylation of the epsilon-amino group of K40 in alpha-tubulin is one such modification that is highly conserved in ciliated organisms. Recently, alpha TAT1, a Gcn5-related N-acetyltransferase, was identified as an alpha-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 alpha-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, alpha TAT1 has a conserved function as the major alpha-tubulin acetyltransferase in ciliated organisms and has an important role in regulating subcellular specialization of subsets of microtubules.