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])
ISSN2211-1247
卷号21期号:13页码:3781-3793
发表状态已发表
DOI10.1016/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
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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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