title: Elongator controls the migration and differentiation of cortical neurons through acetylation of alpha-tubulin.
abstract: The generation of cortical projection neurons relies on the coordination of radial migration with branching. Here, we report that the multisubunit histone acetyltransferase Elongator complex, which contributes to transcript elongation, also regulates the maturation of projection neurons. Indeed, silencing of its scaffold (Elp1) or catalytic subunit (Elp3) cell-autonomously delays the migration and impairs the branching of projection neurons. Strikingly, neurons defective in Elongator show reduced levels of acetylated alpha-tubulin. Reduction of alpha-tubulin acetylation via expression of a nonacetylatable alpha-tubulin mutant leads to comparable defects in cortical neurons and suggests that alpha-tubulin is a target of Elp3. This is further supported by the demonstration that Elp3 promotes acetylation and counteracts HDAC6-mediated deacetylation of this substrate in vitro. Our results uncover alpha-tubulin as a target of the Elongator complex and suggest that a tight regulation of its acetylation underlies the maturation of cortical projection neurons.
authors.affiliation: GIGA-Signal Transduction, University of Liege, C.H.U. Sart Tilman, 4000 Liège, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Creppe
authors.forename: Lina
authors.initials: L
authors.lastname: Malinouskaya
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Volvert
authors.forename: Magali
authors.initials: M
authors.lastname: Gillard
authors.forename: Pierre
authors.initials: P
authors.lastname: Close
authors.forename: Olivier
authors.initials: O
authors.lastname: Malaise
authors.forename: Sophie
authors.initials: S
authors.lastname: Laguesse
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cornez
authors.forename: Souad
authors.initials: S
authors.lastname: Rahmouni
authors.forename: Sandra
authors.initials: S
authors.lastname: Ormenese
authors.forename: Shibeshih
authors.initials: S
authors.lastname: Belachew
authors.forename: Brigitte
authors.initials: B
authors.lastname: Malgrange
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Chapelle
authors.forename: Ulrich
authors.initials: U
authors.lastname: Siebenlist
authors.forename: Gustave
authors.initials: G
authors.lastname: Moonen
authors.forename: Alain
authors.initials: A
authors.lastname: Chariot
authors.forename: Laurent
authors.initials: L
authors.lastname: Nguyen
mesh_terms: D000107:Acetylation; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology*; D014404:Tubulin / Q000378:metabolism*
chemical_list: D009097:Multienzyme Complexes; D014404:Tubulin; D051548:Histone Acetyltransferases