Elongator Controls the Migration and Differentiation of Cortical Neurons Through Acetylation of Alpha-Tubulin

Cell. 2009 Feb 6;136(3):551-64. doi: 10.1016/j.cell.2008.11.043. Epub 2009 Jan 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Cell Line
  • Cell Movement*
  • Cells, Cultured
  • Cerebral Cortex / cytology*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Female
  • Histone Acetyltransferases / metabolism*
  • Humans
  • Mice
  • Multienzyme Complexes / metabolism
  • Neurogenesis
  • Neurons / cytology*
  • Tubulin / metabolism*

Substances

  • Multienzyme Complexes
  • Tubulin
  • Histone Acetyltransferases