Nuclear translocation of CAM-associated protein activates transcription for long-term facilitation in Aplysia

Cell. 2007 May 18;129(4):801-12. doi: 10.1016/j.cell.2007.03.041.


Repeated pulses of serotonin (5-HT) induce long-term facilitation (LTF) of the synapses between sensory and motor neurons of the gill-withdrawal reflex in Aplysia. To explore how apCAM downregulation at the plasma membrane and CREB-mediated transcription in the nucleus, both of which are required for the formation of LTF, might relate to each other, we cloned an apCAM-associated protein (CAMAP) by yeast two-hybrid screening. We found that 5-HT signaling at the synapse activates PKA which in turn phosphorylates CAMAP to induce the dissociation of CAMAP from apCAM and the subsequent translocation of CAMAP into the nucleus of sensory neurons. In the nucleus, CAMAP acts as a transcriptional coactivator for CREB1 and is essential for the activation of ApC/EBP required for the initiation of LTF. Combined, our data suggest that CAMAP is a retrograde signaling component that translocates from activated synapses to the nucleus during synapse-specific LTF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Aplysia / cytology
  • Aplysia / metabolism*
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / isolation & purification
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Enhancer Elements, Genetic / physiology
  • Humans
  • Long-Term Potentiation / physiology*
  • Nervous System / cytology
  • Nervous System / metabolism*
  • Neurons, Afferent / metabolism*
  • Serotonin / metabolism
  • Synaptic Transmission / physiology
  • Transcriptional Activation / physiology


  • Cell Adhesion Molecules, Neuronal
  • Cyclic AMP Response Element-Binding Protein
  • Serotonin
  • Cyclic AMP-Dependent Protein Kinases