A calcium-regulated MEF2 surnoylation switch controls postsynaptic differentiation
A calcium-regulated MEF2 surnoylation switch controls postsynaptic differentiation
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DOI：
10.1126/science.1122513
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发表时间：
2006-02-17
期刊：
影响因子：
56.9
通讯作者：
Bonni, A
中科院分区：
文献类型：
--
作者：
Shalizi, A;Gaudillière, B;Bonni, A
突触后树突分化是突触形成过程中必不可少的一步。在此，我们报道了在小脑皮质突触后颗粒神经元树突状爪的形态发生中对转录因子肌细胞增强因子2A(MEF2A)的需求。一种转录抑制形式的MEF2a，在赖氨酸-403处被总和甲基化，促进树突爪的分化。活性依赖性钙信号诱导钙调神经磷酸酶介导的MEF2A在丝氨酸-408处去磷酸化，从而促进在赖氨酸-403处从苏莫化到乙酰化的转换，从而抑制树突状细胞的爪状分化。我们的发现定义了突触后分化的潜在机制，该机制可能调节大脑中依赖活动的突触发育和可塑性。
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.