title: Mice lacking α-tubulin acetyltransferase 1 are viable but display α-tubulin acetylation deficiency and dentate gyrus distortion.
abstract: α-Tubulin acetylation at Lys-40, located on the luminal side of microtubules, has been widely studied and used as a marker for stable microtubules in the cilia and other subcellular structures, but the functional consequences remain perplexing. Recent studies have shown that Mec-17 and its paralog are responsible for α-tubulin acetylation in Caenorhabditis elegans. There is one such protein known as Atat1 (α-tubulin acetyltransferase 1) per higher organism. Zebrafish Atat1 appears to govern embryo development, raising the intriguing possibility that Atat1 is also critical for development in mammals. In addition to Atat1, three other mammalian acetyltransferases, ARD1-NAT1, ELP3, and GCN5, have been shown to acetylate α-tubulin in vitro, so an important question is how these four enzymes contribute to the acetylation in vivo. We demonstrate here that Atat1 is a major α-tubulin acetyltransferase in mice. It is widely expressed in mouse embryos and tissues. Although Atat1-null animals display no overt phenotypes, α-tubulin acetylation is lost in sperm flagella and the dentate gyrus is slightly deformed. Furthermore, human ATAT1 colocalizes on bundled microtubules with doublecortin. These results thus suggest that mouse Atat1 may regulate advanced functions such as learning and memory, thereby shedding novel light on the physiological roles of α-tubulin acetylation in mammals.
authors.affiliation: Rosalind and Morris Goodman Cancer Research Center, Montréal, Québec H3A 1A3, Canada.
authors.forename: Go-Woon
authors.initials: GW
authors.lastname: Kim
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ghorbani
authors.forename: Linya
authors.initials: L
authors.lastname: You
authors.forename: Xiang-Jiao
authors.initials: XJ
authors.lastname: Yang
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000002:abnormalities / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008868:Microtubule Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013082:Sperm Tail / Q000378:metabolism; D013737:Testis / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism*
chemical_list: D008868:Microtubule Proteins; D014404:Tubulin; D000123:Acetyltransferases; C583619:ATAT1 protein, mouse; C049182:alpha-tubulin acetylase
keywords: Histone Acetylase; Histone Deacetylase; Lysine Acetylation; Microtubules; Mouse Genetics; Neural Stem Cell; Post-translational Modification; Tubulin; Tubulin Acetylation; Tubulin Acetyltransferase