αTAT1 is the major α-tubulin acetyltransferase in mice

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.