Microtubule acetylation by αTAT1 is essential for touch sensation in zebrafish but dispensable for embryonic development.

Acetylation of α-tubulin at lysine 40 (α-tub(K40Ac)) is a conserved post-translational modification that occurs on the microtubule lumenal surface, but its developmental functions remain poorly defined. In zebrafish, morpholino knockdown of α-tubulin acetyltransferase 1 (αTAT1), the enzyme responsible for depositing α-tub(K40Ac) marks, has been reported to cause severe developmental defects, whereas genetic loss-of-function studies in mice found no overt role in development. Here, we generated αTAT1 loss-of-function alleles in zebrafish and found that, in contrast to morphants, mutants are viable, fertile, and develop normally. αTAT1 mutants lack detectable α-tub(K40Ac) in all examined tissues, indicating that no other enzyme compensates for loss of αTAT1. Both cilia and neurons normally display high levels of α-tub(K40Ac) and despite the complete loss of this modification in αTAT1 mutants, gross cilia structure and motility were preserved, and cilia-dependent developmental processes remained intact. However, αTAT1 mutants did exhibit defects in touch responsiveness, something which could be rescued by wild-type but not catalytically inactive αTAT1. These findings demonstrate that αTAT1 is solely responsible for α-tub(K40Ac) in zebrafish and that, while dispensable for embryonic development and ciliary function, this modification is required for normal somatosensory behavior.