α-Tubulin acetylation at lysine 40 regulates dendritic arborization and larval locomotion by promoting microtubule stability in Drosophila

Abstract

Posttranslational modification of tubulin increases the dynamic complexity and functional diversity of microtubules. Acetylation of α-tubulin at Lys-40 is a highly conserved posttranslational modification that has been shown to improve the flexibility and resilience of microtubules. Here we studied thein vivofunctions of α-tubulin acetylation by knocking-out Atat, theDrosophilaα-tubulin acetyltransferase, and by mutating Lys-40 to Arg in α1-tubulin. We found a reduction in the dendritic arborization of larval class I dendritic arborization (da) neurons in both mutants. The dendritic developmental defects inatatmutants could be reversed by enhancing the stability of microtubules either through knocking down the microtubule severing protein Katanin 60 or through overexpressing tubulin-specific chaperone E, suggesting that α-tubulin deacetylation impairsed dendritic morphology by decreasing the stability of microtubules. Using time-lapse recordings, we found thatatatandα1-tubulinK40Rmutations dramatically increased the number of dendritic protrusions that were likely to be immature dendritic precursors. Finally, we showed that both Atat and α-tubulin acetylation were required in class I da neurons to control larval locomotion. These findings add novel insight into the current knowledge of the role of α-tubulin acetylation in regulating neuronal development and functions.