Effects of mutating α-tubulin lysine 40 on sensory dendrite development

Microtubules are essential for neuronal structure and function. Axonal and dendritic microtubules are enriched in post-translational modifications that impact microtubule dynamics, transport and microtubule-associated proteins. Acetylation of alpha-tubulin lysine 40 (K40) is a prominent and conserved modification of neuronal microtubules. However, the cellular role of microtubule acetylation remains controversial. To resolve how microtubule acetylation might affect neuronal morphogenesis, we mutated endogenous alpha-tubulin in vivo using a new Drosophila strain that facilitates the rapid knock-in of designer alpha Tub84B alleles (the predominant alpha-tubulin-encoding gene in flies). Leveraging our new strain, we found that microtubule acetylation, as well as polyglutamylation and (de) tyrosination, is not essential for survival. However, we found that dendrite branch refinement in sensory neurons relies on alpha-tubulin K40. Mutagenesis of K40 reveals moderate yet significant changes in dendritic lysosome transport, microtubule polymerization and Futsch protein distribution in dendrites but not in axons. Our studies point to an unappreciated role for alpha-tubulin K40 and acetylation in dendrite morphogenesis. While our results are consistent with the idea that acetylation tunes microtubule function within neurons, they also suggest there may be an acetylation-independent requirement for alpha-tubulin K40. This article has an associated First Person interview with the first author of the paper.