A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation

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

Aryaman Shalizi ¹, Brice Gaudillière, Zengqiang Yuan, Judith Stegmüller, Takahiro Shirogane, Qingyuan Ge, Yi Tan, Brenda Schulman, J Wade Harper, Azad Bonni

Affiliations

Affiliation

1 Department of Pathology, Harvard Medical School, 77 Louis Pasteur Avenue, Boston, MA 02115, USA.

PMID: 16484498 DOI: 10.1126/science.1122513

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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