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.

Original languageEnglish
Pages (from-to)1012-1017
Number of pages6
JournalScience
Volume311
Issue number5763
DOIs
StatePublished - Feb 17 2006

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    Shalizi, A., Gaudillière, B., Yuan, Z., Stegmüller, J., Shirogane, T., Ge, Q., Tan, Y., Schulman, B., Harper, J. W., & Bonni, A. (2006). A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation. Science, 311(5763), 1012-1017. https://doi.org/10.1126/science.1122513