A Calcium-Regulated MEF2 Sumoylation Switch Controls Postsynaptic Differentiation

• DOI: 10.1126/science.1122513
• Publication Date: 2006-02-16T21:43:19Z
• Authors: Aryaman Shalizi; Brice Gaudillière; Zengqiang Yuan; Judith Stegmüller; Takahiro Shirogane; Qingyuan Ge; Yi Tan; Brenda Schulman; J. Wade Harper; Azad Bonni
• Keywords: Neurons; 0303 health sciences; MEF2 Transcription Factors; Calcineurin; Recombinant Fusion Proteins; Acetylation; Cell Differentiation; Dendrites; In Vitro Techniques; Cell Line; Rats; Cerebellar Cortex; 03 medical and health sciences; Electroporation; Myogenic Regulatory Factors; Morphogenesis; Animals; Humans; Calcium; RNA Interference; Calcium Signaling; Phosphorylation

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.