Tubulin Acetyltransferase αTAT1 Destabilizes Microtubules Independently of Its Acetylation Activity

Acetylation of alpha-tubulin at lysine 40 (K40) is a well-conserved posttranslational modification that marks long-lived microtubules but has poorly understood functional significance. Recently, alpha TAT1, a member of the Gcn5-relatedN-acetyltransferase superfamily, has been identified as an alpha-tubulin acetyltransferase in ciliated organisms. Here, we explored the function of alpha TAT1 with the aim of understanding the consequences of alpha TAT1-mediated microtubule acetylation. We demonstrate that alpha-tubulin is the major target of alpha TAT1 but that alpha TAT1 also acetylates itself in a regulatory mechanism that is required for effective modification of tubulin. We further show that in mammalian cells, alpha TAT1 promotes microtubule destabilization and accelerates microtubule dynamics. Intriguingly, this effect persists in an alpha TAT1 mutant with no acetyltransferase activity, suggesting that interaction of alpha TAT1 with microtubules, rather than acetylation per se, is the critical factor regulating microtubule stability. Our data demonstrate that alpha TAT1 has cellular functions that extend beyond its classical enzymatic activity as an alpha-tubulin acetyltransferase.