Tubulin acetyltransferase ?TAT1 destabilizes microtubules independently of its acetylation activity.

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

SUBMITTER: Kalebic N 

PROVIDER: S-EPMC3592022 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature