Microtubule acetylation by ⍺TAT1 is essential for touch sensation in zebrafish but dispensable for embryonic development.

Acetylation of ⍺-tubulin at lysine 40 (⍺-tubK40Ac) 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 ⍺-tubulin acetyltransferase 1 (⍺TAT1), the enzyme responsible for depositing ⍺-tubK40Ac 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 ⍺TAT1 loss-of-function alleles in zebrafish and found that, in contrast to morphants, mutants are viable, fertile, and develop normally. ⍺TAT1 mutants lack detectable ⍺-tubK40Ac in all examined tissues, indicating that no other enzyme compensates for loss of ⍺TAT1. Both cilia and neurons normally display high levels of ⍺-tubK40Ac and despite the complete loss of this modification in ⍺TAT1 mutants, gross cilia structure and motility were preserved, and cilia-dependent developmental processes remained intact. However, ⍺TAT1 mutants did exhibit defects in touch responsiveness, something which could be rescued by wild-type but not catalytically inactive ⍺TAT1. These findings demonstrate that ⍺TAT1 is solely responsible for ⍺-tubK40Ac in zebrafish and that, while dispensable for embryonic development and ciliary function, this modification is required for normal somatosensory behavior.