title: αTAT1 is the major α-tubulin acetyltransferase in mice.
abstract: Post-translational modification of tubulin serves as a powerful means for rapidly adjusting the functional diversity of microtubules. Acetylation of the ε-amino group of K40 in α-tubulin is one such modification that is highly conserved in ciliated organisms. Recently, αTAT1, a Gcn5-related N-acetyltransferase, was identified as an α-tubulin acetyltransferase in Tetrahymena and C. elegans. Here we generate mice with a targeted deletion of Atat1 to determine its function in mammals. Remarkably, we observe a loss of detectable K40 α-tubulin acetylation in these mice across multiple tissues and in cellular structures such as cilia and axons where acetylation is normally enriched. Mice are viable and develop normally, however, the absence of Atat1 impacts upon sperm motility and male mouse fertility, and increases microtubule stability. Thus, αTAT1 has a conserved function as the major α-tubulin acetyltransferase in ciliated organisms and has an important role in regulating subcellular specialization of subsets of microtubules.
authors.affiliation: Mouse Biology Unit, EMBL, Via Ramarini 32, Monterotondo 00015, Italy.
authors.forename: Nereo
authors.initials: N
authors.lastname: Kalebic
authors.forename: Simona
authors.initials: S
authors.lastname: Sorrentino
authors.forename: Emerald
authors.initials: E
authors.lastname: Perlas
authors.forename: Giulia
authors.initials: G
authors.lastname: Bolasco
authors.forename: Concepcion
authors.initials: C
authors.lastname: Martinez
authors.forename: Paul A
authors.initials: PA
authors.lastname: Heppenstall
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000123:Acetyltransferases / Q000172:deficiency / Q000378:metabolism*; D000483:Alleles; D000818:Animals; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D056426:Genetic Loci / Q000235:genetics; D016678:Genome / Q000235:genetics; D008239:Lysine / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008868:Microtubule Proteins; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D010641:Phenotype; D058105:Polymerization / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*
chemical_list: D008868:Microtubule Proteins; D014404:Tubulin; D000123:Acetyltransferases; C583619:ATAT1 protein, mouse; D008239:Lysine; D015739:Nocodazole