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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
Abstract:
Postsynaptic differentiation of dendrites is an essential stepin synapse formation. We report here a requirement for the transcriptionfactor myocyte enhancer factor 2A (MEF2A) in the morphogenesisof postsynaptic granule neuron dendritic claws in the cerebellarcortex. A transcriptional repressor form of MEF2A that is sumoylatedat lysine-403 promoted dendritic claw differentiation. Activity-dependentcalcium signaling induced a calcineurin-mediated dephosphorylationof MEF2A at serine-408 and, thereby, promoted a switch fromsumoylation to acetylation at lysine-403, which led to inhibitionof dendritic claw differentiation. Our findings define a mechanismunderlying postsynaptic differentiation that may modulate activity-dependentsynapse 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.
To whom correspondence should be addressed. E-mail: azad_bonni{at}hms.harvard.edu
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