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题名

IRSp53 promotes postsynaptic density formation and actin filament bundling

作者
通讯作者Kim,Eunjoon; Zhang,Mingjie
发表日期
2022-08-01
DOI
发表期刊
ISSN
0021-9525
EISSN
1540-8140
卷号221期号:8
摘要
IRSp53 (aka BAIAP2) is a scaffold protein that couples membranes with the cytoskeleton in actin-filled protrusions such as filopodia and lamellipodia. The protein is abundantly expressed in excitatory synapses and is essential for synapse development and synaptic plasticity, although with poorly understood mechanisms. Here we show that specific multivalent interactions between IRSp53 and its binding partners PSD-95 or Shank3 drive phase separation of the complexes in solution. IRSp53 can be enriched to the reconstituted excitatory PSD (ePSD) condensates via bridging to the core and deeper layers of ePSD. Overexpression of a mutant defective in the IRSp53/PSD-95 interaction perturbs synaptic enrichment of IRSp53 in mouse cortical neurons. The reconstituted PSD condensates promote bundled actin filament formation both in solution and on membranes, via IRSp53-mediated actin binding and bundling. Overexpression of mutants that perturb IRSp53-actin interaction leads to defects in synaptic maturation of cortical neurons. Together, our studies provide potential mechanistic insights into the physiological roles of IRSp53 in synapse formation and function.
相关链接[Scopus记录]
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语种
英语
重要成果
NI论文
学校署名
通讯
资助项目
National Natural Science Foundation of China[82188101];Human Frontier Science Program[RGP0020/2019];
WOS研究方向
Cell Biology
WOS类目
Cell Biology
WOS记录号
WOS:000868315400001
出版者
ESI学科分类
MOLECULAR BIOLOGY & GENETICS
Scopus记录号
2-s2.0-85134427019
来源库
Scopus
引用统计
被引频次[WOS]:11
成果类型期刊论文
条目标识符http://sustech.caswiz.com/handle/2SGJ60CL/359548
专题生命科学学院
作者单位
1.Division of Life Science,State Key Laboratory of Molecular Neuroscience,Hong Kong University of Science and Technology,Hong Kong,China
2.State Key Laboratory of Genetic Engineering,School of Life Sciences,Fudan University,China
3.Center for Synaptic Brain Dysfunctions,Institute for Basic Science (IBS),South Korea
4.Department of Biological Sciences,Korea Advanced Institute of Science and Technology (KAIST),South Korea
5.School of Life Sciences,Southern University of Science and Technology,Shenzhen,China
通讯作者单位生命科学学院
推荐引用方式
GB/T 7714
Feng,Zhe,Lee,Suho,Jia,Bowen,et al. IRSp53 promotes postsynaptic density formation and actin filament bundling[J]. JOURNAL OF CELL BIOLOGY,2022,221(8).
APA
Feng,Zhe,Lee,Suho,Jia,Bowen,Jian,Tao,Kim,Eunjoon,&Zhang,Mingjie.(2022).IRSp53 promotes postsynaptic density formation and actin filament bundling.JOURNAL OF CELL BIOLOGY,221(8).
MLA
Feng,Zhe,et al."IRSp53 promotes postsynaptic density formation and actin filament bundling".JOURNAL OF CELL BIOLOGY 221.8(2022).
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