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首页> 外文期刊>Neuron >Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation.
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Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation.

机译：MeCP2的大脑特异性磷酸化调节活性依赖的Bdnf转录，树突状生长和脊柱成熟。

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Mutations or duplications in MECP2 cause Rett and Rett-like syndromes, neurodevelopmental disorders characterized by mental retardation, motor dysfunction, and autistic behaviors. MeCP2 is expressed in many mammalian tissues and functions as a global repressor of transcription; however, the molecular mechanisms by which MeCP2 dysfunction leads to the neural-specific phenotypes of RTT remain poorly understood. Here, we show that neuronal activity and subsequent calcium influx trigger the de novo phosphorylation of MeCP2 at serine 421 (S421) by a CaMKII-dependent mechanism. MeCP2 S421 phosphorylation is induced selectively in the brain in response to physiological stimuli. Significantly, we find that S421 phosphorylation controls the ability of MeCP2 to regulate dendritic patterning, spine morphogenesis, and the activity-dependent induction of Bdnf transcription. These findings suggest that, by triggering MeCP2 phosphorylation, neuronal activity regulates a program of gene expression that mediates nervous system maturation and that disruption of this process in individuals with mutations in MeCP2 may underlie the neural-specific pathology of RTT.
机译：MECP2中的突变或重复会引起Rett和Rett-like综合征，以智力低下，运动功能障碍和自闭症行为为特征的神经发育障碍。 MeCP2在许多哺乳动物组织中表达，并起着全局转录阻遏物的作用。然而，MeCP2功能障碍导致RTT的神经特异性表型的分子机制仍然知之甚少。在这里，我们显示神经元活动和随后的钙内流通过CaMKII依赖性机制触发了丝氨酸421（S421）上MeCP2的从头磷酸化。响应生理刺激，MeCP2 S421磷酸化在大脑中被选择性诱导。重要的是，我们发现S421磷酸化控制MeCP2调节树突模式，脊柱形态发生和Bdnf转录的活性依赖诱导的能力。这些发现表明，通过触发MeCP2磷酸化，神经元活性调节了介导神经系统成熟的基因表达程序，并且在具有MeCP2突变的个体中这一过程的破坏可能是RTT神经特异性病理的基础。

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