title: Tubulin acetyltransferase αTAT1 destabilizes microtubules independently of its acetylation activity.
abstract: Acetylation of α-tubulin at lysine 40 (K40) is a well-conserved posttranslational modification that marks long-lived microtubules but has poorly understood functional significance. Recently, αTAT1, a member of the Gcn5-related N-acetyltransferase superfamily, has been identified as an α-tubulin acetyltransferase in ciliated organisms. Here, we explored the function of αTAT1 with the aim of understanding the consequences of αTAT1-mediated microtubule acetylation. We demonstrate that α-tubulin is the major target of αTAT1 but that αTAT1 also acetylates itself in a regulatory mechanism that is required for effective modification of tubulin. We further show that in mammalian cells, αTAT1 promotes microtubule destabilization and accelerates microtubule dynamics. Intriguingly, this effect persists in an αTAT1 mutant with no acetyltransferase activity, suggesting that interaction of αTAT1 with microtubules, rather than acetylation per se, is the critical factor regulating microtubule stability. Our data demonstrate that αTAT1 has cellular functions that extend beyond its classical enzymatic activity as an α-tubulin acetyltransferase.
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory, Monterotondo, Rome, Italy.
authors.forename: Nereo
authors.initials: N
authors.lastname: Kalebic
authors.forename: Concepcion
authors.initials: C
authors.lastname: Martinez
authors.forename: Emerald
authors.initials: E
authors.lastname: Perlas
authors.forename: Philip
authors.initials: P
authors.lastname: Hublitz
authors.forename: Daniel
authors.initials: D
authors.lastname: Bilbao-Cortes
authors.forename: Karol
authors.initials: K
authors.lastname: Fiedorczuk
authors.forename: Annapaola
authors.initials: A
authors.lastname: Andolfo
authors.forename: Paul A
authors.initials: PA
authors.lastname: Heppenstall
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D008239:Lysine / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000201:enzymology / Q000378:metabolism*; D041681:NIH 3T3 Cells; D014404:Tubulin / Q000378:metabolism*
chemical_list: D014404:Tubulin; D000123:Acetyltransferases; C049182:alpha-tubulin acetylase; D008239:Lysine