典型文献
Loss of O-GlcNAcylation on MeCP2 at Threonine 203 Leads to Neurodevelopmental Disorders
文献摘要：
Mutations of the X-linked methyl-CpG-binding protein 2(MECP2)gene in humans are responsible for most cases of Rett syndrome(RTT),an X-linked progres-sive neurological disorder.While genome-wide screens in clinical trials have revealed several putative RTT-associ-ated mutations in MECP2,their causal relevance regarding the functional regulation of MeCP2 at the etiologic sites at the protein level requires more evidence.In this study,we demonstrated that MeCP2 was dynamically modified by O-linked-β-N-acetylglucosamine(O-GlcNAc)at threonine 203(T203),an etiologic site in RTT patients.Disruption of the O-GlcNAcylation of MeCP2 specifically at T203 impaired dendrite development and spine maturation in cultured hippocampal neurons,and disrupted neuronal migration,dendritic spine morphogenesis,and caused dysfunction of synaptic transmission in the developing and juvenile mouse cerebral cortex.Mechanistically,genetic disruption of O-GlcNAcylation at T203 on MeCP2 decreased the neuronal activity-induced induction of Bdnf transcription.Our study highlights the critical role of MeCP2 T2O3 O-GlcNAcylation in neural development and synaptic transmission potentially via brain-derived neu-rotrophic factor.
文献关键词：
中图分类号：
作者姓名：
Juanxian Cheng;Zhe Zhao;Liping Chen;Ying Li;Ruijing Du;Yan Wu;Qian Zhu;Ming Fan;Xiaotao Duan;Haitao Wu
作者机构：
Department of Neurobiology,Beijing Institute of Basic Medical Sciences,Beijing 100850,China;Key Laboratory of Neuroregeneration,Co-innovation Center of Neuroregeneration,Nantong University,Nantong 226019,China;State Key Laboratory of Toxicology and Medical Counter-measures,Beijing Institute of Pharmacology and Toxicology,Beijing 100850,China;Chinese Institute for Brain Research,Beijing 102206,China
文献出处：
引用格式：
[1]Juanxian Cheng;Zhe Zhao;Liping Chen;Ying Li;Ruijing Du;Yan Wu;Qian Zhu;Ming Fan;Xiaotao Duan;Haitao Wu-.Loss of O-GlcNAcylation on MeCP2 at Threonine 203 Leads to Neurodevelopmental Disorders)[J].神经科学通报（英文版）,2022(02):113-134
A类：
Leads,Neurodevelopmental,T203,T2O3,rotrophic
B类：
Loss,GlcNAcylation,MeCP2,Threonine,Disorders,Mutations,linked,methyl,CpG,binding,protein,MECP2,humans,are,responsible,most,cases,Rett,syndrome,RTT,progres,sive,neurological,disorder,While,genome,wide,screens,clinical,trials,have,revealed,several,putative,associ,mutations,their,causal,relevance,regarding,functional,regulation,etiologic,sites,level,requires,more,evidence,In,this,study,we,demonstrated,that,was,dynamically,modified,by,acetylglucosamine,threonine,patients,Disruption,specifically,impaired,dendrite,spine,maturation,cultured,hippocampal,neurons,disrupted,neuronal,migration,dendritic,morphogenesis,caused,dysfunction,synaptic,transmission,developing,juvenile,mouse,cerebral,cortex,Mechanistically,genetic,disruption,decreased,activity,induced,induction,Bdnf,transcription,Our,highlights,critical,role,neural,potentially,via,brain,derived
AB值：
0.613338
相似文献
机标中图分类号，由域田数据科技根据网络公开资料自动分析生成，仅供学习研究参考。
