A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation

Science. 2006 Feb 17;311(5763):1012-7. doi: 10.1126/science.1122513.


Postsynaptic differentiation of dendrites is an essential step in synapse formation. We report here a requirement for the transcription factor myocyte enhancer factor 2A (MEF2A) in the morphogenesis of postsynaptic granule neuron dendritic claws in the cerebellar cortex. A transcriptional repressor form of MEF2A that is sumoylated at lysine-403 promoted dendritic claw differentiation. Activity-dependent calcium signaling induced a calcineurin-mediated dephosphorylation of MEF2A at serine-408 and, thereby, promoted a switch from sumoylation to acetylation at lysine-403, which led to inhibition of dendritic claw differentiation. Our findings define a mechanism underlying postsynaptic differentiation that may modulate activity-dependent synapse development and plasticity in the brain.

Publication types

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

MeSH terms

  • Acetylation
  • Animals
  • Calcineurin / metabolism
  • Calcium / metabolism*
  • Calcium Signaling
  • Cell Differentiation
  • Cell Line
  • Cerebellar Cortex / cytology
  • Cerebellar Cortex / physiology*
  • Dendrites / physiology
  • Dendrites / ultrastructure*
  • Electroporation
  • Humans
  • In Vitro Techniques
  • MEF2 Transcription Factors
  • Morphogenesis
  • Myogenic Regulatory Factors / genetics
  • Myogenic Regulatory Factors / metabolism*
  • Neurons / cytology*
  • Neurons / physiology
  • Phosphorylation
  • RNA Interference
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Synapses / physiology*
  • Transcription, Genetic
  • Transfection


  • MEF2 Transcription Factors
  • Myogenic Regulatory Factors
  • Recombinant Fusion Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • Calcineurin
  • Calcium