Belachew, Shibeshih[Université de Liège - ULg > Département des sciences cliniques > Neurologie - CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc. >]
Malgrange, Brigitte[Université de Liège - ULg > > CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc. - Neurologie >]
Chapelle, Jean-Paul[Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
[en] The generation of cortical projection neurons relies on the coordination of radial migration with branching. Here we report that the multi-subunit 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. A direct reduction of alpha tubulin acetylation 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.
Giga-Signal Transduction ; Giga-Neurosciences
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; TELEVIE ; ARC-ULG ; PAI Phase VI ; Fonds Léon Fredericq (Prix Suez) ; FBC