Postnatal deamidation of 4E-BP2 in brain enhances its association with raptor and alters kinetics of excitatory synaptic transmission

Mol Cell. 2010 Mar 26;37(6):797-808. doi: 10.1016/j.molcel.2010.02.022.


The eIF4E-binding proteins (4E-BPs) repress translation initiation by preventing eIF4F complex formation. Of the three mammalian 4E-BPs, only 4E-BP2 is enriched in the mammalian brain and plays an important role in synaptic plasticity and learning and memory formation. Here we describe asparagine deamidation as a brain-specific posttranslational modification of 4E-BP2. Deamidation is the spontaneous conversion of asparagines to aspartates. Two deamidation sites were mapped to an asparagine-rich sequence unique to 4E-BP2. Deamidated 4E-BP2 exhibits increased binding to the mammalian target of rapamycin (mTOR)-binding protein raptor, which effects its reduced association with eIF4E. 4E-BP2 deamidation occurs during postnatal development, concomitant with the attenuation of the activity of the PI3K-Akt-mTOR signaling pathway. Expression of deamidated 4E-BP2 in 4E-BP2(-/-) neurons yielded mEPSCs exhibiting increased charge transfer with slower rise and decay kinetics relative to the wild-type form. 4E-BP2 deamidation may represent a compensatory mechanism for the developmental reduction of PI3K-Akt-mTOR signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Newborn
  • Brain / metabolism*
  • Cells, Cultured
  • Eukaryotic Initiation Factors / chemistry
  • Eukaryotic Initiation Factors / deficiency
  • Eukaryotic Initiation Factors / genetics
  • Eukaryotic Initiation Factors / metabolism*
  • Humans
  • Kinetics
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Organ Specificity
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Protein Transport
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Synaptic Transmission*


  • Eif4ebp2 protein, mouse
  • Eukaryotic Initiation Factors