A calcium-regulated MEF2 surnoylation switch controls postsynaptic differentiation

被引：367

作者：

Shalizi, A

Gaudillière, B

Yuan, ZQ

Stegmüller, J

Shirogane, T

Ge, QY

Tan, Y

Schulman, B

Harper, JW

Bonni, A

机构：

[1] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA

[3] Cell Signaling Technol Inc, Beverly, MA 01915 USA

[4] St Jude Childrens Hosp, Howard Hughes Med Inst, Dept Biol Struct, Memphis, TN 38105 USA

[5] St Jude Childrens Hosp, Howard Hughes Med Inst, Dept Genet, Memphis, TN 38105 USA

[6] St Jude Childrens Hosp, Howard Hughes Med Inst, Dept Tumor Cell Biol, Memphis, TN 38105 USA

来源：

SCIENCE | 2006年 / 311卷 / 5763期

关键词：

D O I：

10.1126/science.1122513

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 dephosphorytation 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.

引用

页码：1012 / 1017

页数：6

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