Cell cycle-linked MeCP2 phosphorylation modulates adult neurogenesis involving the Notch signalling pathway

Nat Commun. 2014 Nov 25;5:5601. doi: 10.1038/ncomms6601.

Abstract

Neuronal activity regulates the phosphorylation states at multiple sites on MeCP2 in postmitotic neurons. The precise control of the phosphorylation status of MeCP2 in neurons is critical for the normal development and function of the mammalian brain. However, it is unknown whether phosphorylation at any of the previously identified sites on MeCP2 can be induced by signals other than neuronal activity in other cell types, and what functions MeCP2 phosphorylation may have in those contexts. Here we show that in neural progenitor cells isolated from the adult mouse hippocampus, cell cycle-linked phosphorylation at serine 421 on MeCP2 is directly regulated by aurora kinase B and modulates the balance between proliferation and neural differentiation through the Notch signalling pathway. Our findings suggest MeCP2 S421 phosphorylation may function as a general epigenetic switch accessible by different extracellular stimuli through different signalling pathways for regulating diverse biological functions in different cell types.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Aurora Kinase B / genetics
  • Aurora Kinase B / metabolism
  • Cell Cycle
  • Cells, Cultured
  • Female
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Male
  • Methyl-CpG-Binding Protein 2 / chemistry
  • Methyl-CpG-Binding Protein 2 / genetics
  • Methyl-CpG-Binding Protein 2 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neurogenesis*
  • Neurons / cytology
  • Neurons / metabolism*
  • Phosphorylation
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Signal Transduction*
  • Stem Cells / cytology
  • Stem Cells / metabolism

Substances

  • Mecp2 protein, mouse
  • Methyl-CpG-Binding Protein 2
  • Receptors, Notch
  • Aurkb protein, mouse
  • Aurora Kinase B