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A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation.

Aryaman Shalizi·Brice Gaudillière·Zengqiang Yuan·Judith Stegmüller·Takahiro Shirogane·Qingyuan Ge·Yi Tan·Brenda Schulman·J Wade Harper·Azad Bonni
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Abstract

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.

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AcetylationAnimalsCalcineurinCalciumCalcium SignalingCell DifferentiationCell LineCerebellar CortexDendritesElectroporationHumansIn Vitro TechniquesMEF2 Transcription FactorsMorphogenesisMyogenic Regulatory FactorsNeuronsPhosphorylationRNA InterferenceRatsRecombinant Fusion ProteinsSmall Ubiquitin-Related Modifier ProteinsSynapsesTranscription, GeneticTransfectionJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't

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Aryaman Shalizi, Brice Gaudillière, Zengqiang Yuan, Judith Stegmüller, Takahiro Shirogane, Qingyuan Ge, Yi Tan, Brenda Schulman, J Wade Harper, Azad Bonni. 2006-02-17. A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation.. https://doi.org/10.1126/science.1122513

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