A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation.
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.
Shalizi
Aryaman
A
Department of Pathology, Harvard Medical School, 77 Louis Pasteur Avenue, Boston, MA 02115, USA.
Gaudillière
Brice
B
Yuan
Zengqiang
Z
Stegmüller
Judith
J
Shirogane
Takahiro
T
Ge
Qingyuan
Q
Tan
Yi
Y
Schulman
Brenda
B
Harper
J Wade
JW
Bonni
Azad
A
D000107:Acetylation; D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002454:Cell Differentiation; D002460:Cell Line; D002525:Cerebellar Cortex / Q000166:cytology / Q000502:physiology*; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure*; D018274:Electroporation; D006801:Humans; D066298:In Vitro Techniques; D064326:MEF2 Transcription Factors; D009024:Morphogenesis; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D010766:Phosphorylation; D034622:RNA Interference; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection
D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D011993:Recombinant Fusion Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D019703:Calcineurin; D002118:Calcium