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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Animals
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Calcineurin / metabolism
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Calcium / metabolism*
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Calcium Signaling
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Cell Differentiation
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Cell Line
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Cerebellar Cortex / cytology
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Cerebellar Cortex / physiology*
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Dendrites / physiology
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Dendrites / ultrastructure*
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Electroporation
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Humans
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In Vitro Techniques
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MEF2 Transcription Factors
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Morphogenesis
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Myogenic Regulatory Factors / genetics
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Myogenic Regulatory Factors / metabolism*
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Neurons / cytology*
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Neurons / physiology
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Phosphorylation
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RNA Interference
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Rats
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Recombinant Fusion Proteins / metabolism
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Small Ubiquitin-Related Modifier Proteins / metabolism*
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Synapses / physiology*
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Transcription, Genetic
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Transfection
Substances
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MEF2 Transcription Factors
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Myogenic Regulatory Factors
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Recombinant Fusion Proteins
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Small Ubiquitin-Related Modifier Proteins
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Calcineurin
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Calcium