中文版 | English
Title

IRSp53 promotes postsynaptic density formation and actin filament bundling

Author
Corresponding AuthorKim,Eunjoon; Zhang,Mingjie
Publication Years
2022-08-01
DOI
Source Title
ISSN
0021-9525
EISSN
1540-8140
Volume221Issue: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
Important Publications
NI Journal Papers
SUSTech Authorship
Corresponding
Funding Project
National Natural Science Foundation of China[82188101];Human Frontier Science Program[RGP0020/2019];
WOS Research Area
Cell Biology
WOS Subject
Cell Biology
WOS Accession No
WOS:000868315400001
Publisher
ESI Research Field
MOLECULAR BIOLOGY & GENETICS
Scopus EID
2-s2.0-85134427019
Data Source
Scopus
Citation statistics
Cited Times [WOS]:3
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/359548
DepartmentSchool 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 AffilicationSchool 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).
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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