Tubulin acetylation deficiency promotes axonemal turnover and increases cytoplasmic microtubules.

Abstract

Tubulin post-translational modifications regulate microtubule dynamics. Although α-tubulin acetylation has been linked to microtubule stability, how this modification affects the overall organization of cellular microtubules remains obscure. Here, we generated a Chlamydomonas mutant lacking the acetyltransferase αTAT1, which completely abolished α-tubulin K40 acetylation. Surprisingly, the steady-state lengths of normally acetylated structures, axonemes, and rootlets were largely unaffected. αTAT1 was found to localize to the ciliary tip, where it may stabilize the distal axoneme. Consistent with this, loss of acetylation caused an increase in axonemal tubulin turnover, as revealed by dikaryon-fusion assays. Unexpectedly, the atat1-1 mutant displayed an increased number of dynamic cortical microtubules and could regenerate long cilia after amputation, even when protein synthesis was inhibited. Notably, this increase in cortical microtubules required the presence of cilia, as the atat1-1 mutant carrying the ift46-1 mutation, which abolishes ciliogenesis, exhibited normal cortical microtubule levels. Despite these dramatic cytoskeletal changes, cell growth and division remained essentially normal. These findings suggest that acetylation modulates microtubule behavior by regulating axonemal tubulin turnover and cytoplasmic microtubule dynamics, while cellular morphology is buffered against variations in microtubule content.