The major α-tubulin K40 acetyltransferase αTAT1 promotes rapid ciliogenesis and efficient mechanosensation

Long-lived microtubules found in ciliary axonemes, neuronal processes, and migrating cells are marked by alpha-tubulin acetylation on lysine 40, a modification that takes place inside the microtubule lumen. The physiological importance of microtubule acetylation remains elusive. Here, we identify a BBSome-associated protein that we name alpha TAT1, with a highly specific alpha-tubulin K40 acetyl-transferase activity and a catalytic preference for microtubules over free tubulin. In mammalian cells, the catalytic activity of alpha TAT1 is necessary and sufficient for alpha-tubulin K40 acetylation. Remarkably, alpha TAT1 is universally and exclusively conserved in ciliated organisms, and is required for the acetylation of axonemal microtubules and for the normal kinetics of primary cilium assembly. In Caenorhabditis elegans, microtubule acetylation is most prominent in touch receptor neurons (TRNs) and MEC-17, a homolog of alpha TAT1, and its paralog alpha TAT-2 are required for alpha-tubulin acetylation and for two distinct types of touch sensation. Furthermore, in animals lacking MEC-17, alpha TAT-2, and the sole C. elegans K40 alpha-tubulin MEC-12, touch sensation can be restored by expression of an acetyl-mimic MEC-12[K40Q]. We conclude that alpha TAT1 is the major and possibly the sole alpha-tubulin K40 acetyltransferase in mammals and nematodes, and that tubulin acetylation plays a conserved role in several microtubule-based processes.