Title | IRSp53 promotes postsynaptic density formation and actin filament bundling |
Author | |
Corresponding Author | Kim,Eunjoon; Zhang,Mingjie |
Publication Years | 2022-08-01
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DOI | |
Source Title | |
ISSN | 0021-9525
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EISSN | 1540-8140
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Volume | 221Issue:8 |
Abstract | 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. |
URL | [Source Record] |
Indexed By | |
Language | English
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Important Publications | NI Journal Papers
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SUSTech Authorship | Corresponding
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Funding Project | National Natural Science Foundation of China[82188101];Human Frontier Science Program[RGP0020/2019];
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WOS Research Area | Cell Biology
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WOS Subject | Cell Biology
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WOS Accession No | WOS:000868315400001
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Publisher | |
ESI Research Field | MOLECULAR BIOLOGY & GENETICS
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Scopus EID | 2-s2.0-85134427019
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Data Source | Scopus
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Citation statistics |
Cited Times [WOS]:3
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Document Type | Journal Article |
Identifier | http://kc.sustech.edu.cn/handle/2SGJ60CL/359548 |
Department | School of Life Sciences |
Affiliation | 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 |
Corresponding Author Affilication | School of Life Sciences |
Recommended Citation 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).
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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).
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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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