Ube2b-dependent degradation of DNMT3a relieves a transcriptional brake on opiate-induced synaptic and behavioral plasticity
文献类型:期刊论文
作者 | Chen, Zhong-Guo1,2,3; Wang, Yu-Jun2; Chen, Ruo-Song2,4; Geng, Fan3; Gan, Chen-Ling1; Wang, Wei-Sheng2; Liu, Xing2; Zhou, Hu2; He, Ling1; Hu, Gang3 |
刊名 | MOLECULAR PSYCHIATRY |
出版日期 | 2021-04-01 |
卷号 | 26期号:4页码:1162-1177 |
ISSN号 | 1359-4184 |
DOI | 10.1038/s41380-019-0533-y |
通讯作者 | Hu, Gang(ghu@njmu.edu.cn) ; Liu, Jing-Gen(jgliu@simm.ac.cn) |
英文摘要 | Compelling evidence suggests that synaptic structural plasticity, driven by remodeling of the actin cytoskeleton, underlies addictive drugs-induced long-lasting behavioral plasticity. However, the signaling mechanisms leading to actin cytoskeleton remodeling remain poorly defined. DNA methylation is a critical mechanism used to control activity-dependent gene expression essential for long-lasting synaptic plasticity. Here, we provide evidence that DNA methyltransferase DNMT3a is degraded by the E2 ubiquitin-conjugating enzyme Ube2b-mediated ubiquitination in dorsal hippocampus (DH) of rats that repeatedly self-administrated heroin. DNMT3a degradation leads to demethylation in CaMKK1 gene promotor, thereby facilitating CaMKK1 expression and consequent activation of its downstream target CaMKI alpha, an essential regulator of spinogenesis. CaMKK1/CaMKI alpha signaling regulates actin cytoskeleton remodeling in the DH and behavioral plasticity by activation of Rac1 via acting Rac guanine-nucleotide-exchange factor beta PIX. These data suggest that Ube2b-dependent degradation of DNMT3a relieves a transcriptional brake on CaMKK1 gene and thus activates CaMKK1/CaMKI alpha/beta PIX/Rac1 cascade, leading to drug use-induced actin polymerization and behavior plasticity. |
资助项目 | China Postdoctoral Science Foundation[2015M570392] ; National Natural Science Foundation of China (National Science Foundation of China)[81130087] ; National Natural Science Foundation of China (National Science Foundation of China)[81773710] ; National Natural Science Foundation of China (National Science Foundation of China)[81671322] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences (Youth Innovation Promotion Association CAS)[2017334] |
WOS研究方向 | Biochemistry & Molecular Biology ; Neurosciences & Neurology ; Psychiatry |
语种 | 英语 |
出版者 | SPRINGERNATURE |
WOS记录号 | WOS:000632144900010 |
源URL | [http://119.78.100.183/handle/2S10ELR8/295403] |
专题 | 中国科学院上海药物研究所 |
通讯作者 | Hu, Gang; Liu, Jing-Gen |
作者单位 | 1.China Pharmaceut Univ, Dept Pharmacol, Nanjing 210008, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China 3.Nanjing Med Univ, Dept Pharmacol, Nanjing 211166, Peoples R China 4.Univ Chinese Acad Sci, Shanghai 200031, Peoples R China 5.Zhejiang Chinese Med Univ, Clin Med Coll 3, Dept Neurobiol & Acupuncture, Key Lab Acupuncture & Neurobiol Zhejiang Prov, Hangzhou 310053, Peoples R China |
推荐引用方式 GB/T 7714 | Chen, Zhong-Guo,Wang, Yu-Jun,Chen, Ruo-Song,et al. Ube2b-dependent degradation of DNMT3a relieves a transcriptional brake on opiate-induced synaptic and behavioral plasticity[J]. MOLECULAR PSYCHIATRY,2021,26(4):1162-1177. |
APA | Chen, Zhong-Guo.,Wang, Yu-Jun.,Chen, Ruo-Song.,Geng, Fan.,Gan, Chen-Ling.,...&Liu, Jing-Gen.(2021).Ube2b-dependent degradation of DNMT3a relieves a transcriptional brake on opiate-induced synaptic and behavioral plasticity.MOLECULAR PSYCHIATRY,26(4),1162-1177. |
MLA | Chen, Zhong-Guo,et al."Ube2b-dependent degradation of DNMT3a relieves a transcriptional brake on opiate-induced synaptic and behavioral plasticity".MOLECULAR PSYCHIATRY 26.4(2021):1162-1177. |
入库方式: OAI收割
来源:上海药物研究所
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