Synaptic activity controls localization and function of CtBP1 via binding to Bassoon and Piccolo

EMBO J. 2015 Apr 15;34(8):1056-77. doi: 10.15252/embj.201488796. Epub 2015 Feb 4.


Persistent experience-driven adaptation of brain function is associated with alterations in gene expression patterns, resulting in structural and functional neuronal remodeling. How synaptic activity-in particular presynaptic performance-is coupled to gene expression in nucleus remains incompletely understood. Here, we report on a role of CtBP1, a transcriptional co-repressor enriched in presynapses and nuclei, in the activity-driven reconfiguration of gene expression in neurons. We demonstrate that presynaptic and nuclear pools of CtBP1 are interconnected and that both synaptic retention and shuttling of CtBP1 between cytoplasm and nucleus are co-regulated by neuronal activity. Finally, we show that CtBP1 is targeted and/or anchored to presynapses by direct interaction with the active zone scaffolding proteins Bassoon and Piccolo. This association is regulated by neuronal activity via modulation of cellular NAD/NADH levels and restrains the size of the CtBP1 pool available for nuclear import, thus contributing to the control of activity-dependent gene expression. Our combined results reveal a mechanism for coupling activity-induced molecular rearrangements in the presynapse with reconfiguration of neuronal gene expression.

Keywords: cellular NAD/NADH balance; neuronal activity‐regulated gene expression; neuronal plasticity; presynapse‐to‐nucleus signaling; synapto‐nuclear shuttling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cytoskeletal Proteins / metabolism*
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Neuropeptides / metabolism*
  • Protein Binding
  • Protein Transport
  • Rats
  • Rats, Wistar
  • Synapses / metabolism*
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*


  • Bsn protein, rat
  • Carrier Proteins
  • Ctbp1 protein, rat
  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • Pclo protein, rat
  • Transcription Factors