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Science 311 (5763): 1012-1017

Copyright © 2006 by the American Association for the Advancement of Science

A Calcium-Regulated MEF2 Sumoylation Switch Controls Postsynaptic Differentiation

Aryaman Shalizi,1,2* Brice Gaudillière,1,2* Zengqiang Yuan,1 Judith Stegmüller,1 Takahiro Shirogane,1 Qingyuan Ge,3 Yi Tan,3 Brenda Schulman,4 J. Wade Harper,1 Azad Bonni1,2{dagger}

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.

1 Department of Pathology, Harvard Medical School, 77 Louis Pasteur Avenue, Boston, MA 02115, USA.
2 Program in Biological and Biomedical Sciences, Harvard Medical School, 77 Louis Pasteur Avenue, Boston, MA 02115, USA.
3 Cell Signaling Technology, Inc., 166B Cummings Center, Beverly, MA 01915, USA.
4 Howard Hughes Medical Institute, Departments of Structural Biology and Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105–2794, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: azad_bonni{at}hms.harvard.edu


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