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Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs | |
2017-12-26 | |
发表期刊 | CELL REPORTS (IF:7.5[JCR-2023],8.5[5-Year]) |
ISSN | 2211-1247 |
卷号 | 21期号:13页码:3781-3793 |
发表状态 | 已发表 |
DOI | 10.1016/j.celrep.2017.11.107 |
摘要 | The PSD-95/SAPAP/Shank complex functions as the major scaffold in orchestrating the formation and plasticity of the post-synaptic densities (PSDs). We previously demonstrated that the exquisitely specific SAPAP/Shank interaction is critical for Shank synaptic targeting and Shank-mediated synaptogenesis. Here, we show that the PSD-95/SAPAP interaction, SAPAP synaptic targeting, and SAPAP-mediated synaptogenesis require phosphorylation of the N-terminal repeat sequences of SAPAPs. The atomic structure of the PSD-95 guanylate kinase (GK) in complex with a phosphor-SAPAP repeat peptide, together with biochemical studies, reveals the molecular mechanism underlying the phosphorylation-dependent PSD-95/SAPAP interaction, and it also provides an explanation of a PSD-95 mutation found in patients with intellectual disabilities. Guided by the structural data, we developed potent non-phosphorylated GK inhibitory peptides capable of blocking the PSD-95/SAPAP interaction and interfering with PSD-95/SAPAP-mediated synaptic maturation and strength. These peptides are genetically encodable for investigating the functions of the PSD-95/SAPAP interaction in vivo. |
收录类别 | SCI |
语种 | 英语 |
资助项目 | 973 program grant from Minister of Science and Technology of China[2014CB910204] |
WOS研究方向 | Cell Biology |
WOS类目 | Cell Biology |
WOS记录号 | WOS:000418721800015 |
出版者 | CELL PRESS |
WOS关键词 | POSTSYNAPTIC DENSITY PROTEINS ; AUTISM SPECTRUM DISORDERS ; KINASE-ASSOCIATED PROTEIN ; DENDRITIC SPINES ; AMPA RECEPTORS ; INTELLECTUAL DISABILITY ; PSYCHIATRIC-DISORDERS ; SCAFFOLDING PROTEINS ; EXCITATORY SYNAPSES ; RECOGNITION MODE |
原始文献类型 | Article |
引用统计 | 正在获取...
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文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/16215 |
专题 | 生命科学与技术学院 生命科学与技术学院_特聘教授组_张荣光组 生命科学与技术学院_硕士生 生命科学与技术学院_博士生 |
通讯作者 | Zhang, Mingjie |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai, CAS Ctr Excellence Mol Cell Sci, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 333 Haike Rd, Shanghai 201203, Peoples R China 3.Hong Kong Univ Sci & Technol, Div Life Sci, State Key Lab Mol Neurosci, Kowloon, Hong Kong, Peoples R China 4.Huazhong Univ Sci & Technol, Sch Basic Med, Dept Physiol, Wuhan 4030030, Hubei, Peoples R China 5.Huazhong Univ Sci & Technol, Tongji Med Coll, Wuhan 4030030, Hubei, Peoples R China 6.Huazhong Univ Sci & Technol, Inst Brain Res, Collaborat Innovat Ctr Brain Sci, Wuhan 430030, Hubei, Peoples R China 7.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China 8.Hong Kong Univ Sci & Technol, Dept Chem, Kowloon, Hong Kong, Peoples R China 9.Univ Western Ontario, Siebens Drake Med Res Inst, Schulich Sch Med & Dent, Dept Biochem, London, ON N6A 5C1, Canada 10.MIT, Dept Brain & Cognit Sci, McGovern Inst Brain Res, E25-618, Cambridge, MA 02139 USA 11.Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA 12.Hong Kong Univ Sci & Technol, Ctr Syst Biol & Human Hlth, Kowloon, Hong Kong, Peoples R China |
推荐引用方式 GB/T 7714 | Zhu, Jinwei,Zhou, Qingqing,Shang, Yuan,et al. Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs[J]. CELL REPORTS,2017,21(13):3781-3793. |
APA | Zhu, Jinwei.,Zhou, Qingqing.,Shang, Yuan.,Li, Hao.,Peng, Mengjuan.,...&Zhang, Mingjie.(2017).Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs.CELL REPORTS,21(13),3781-3793. |
MLA | Zhu, Jinwei,et al."Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs".CELL REPORTS 21.13(2017):3781-3793. |
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