中文版 | English
Title

Arc weakens synapses by dispersing AMPA receptors from postsynaptic density via modulating PSD phase separation

Author
Corresponding AuthorZhang, Mingjie
Publication Years
2022-07-01
DOI
Source Title
ISSN
1001-0602
EISSN
1748-7838
Abstract
In response to stimuli, the immediate early gene product Arc can acutely down-regulate synaptic strength by removing AMPA receptors (AMPARs) from synapses and thus regulate synaptic plasticity. How Arc, a scaffold protein, can specifically facilitate synaptic removal of AMPARs is unknown. We found that Arc directly antagonizes with PSD-95 in binding to TARPs, which are the auxiliary subunits of AMPARs. Arc, in a highly concentration-sensitive manner, acutely disperses TARPs from the postsynaptic density (PSD) condensate formed via phase separation. TARPs with the Ser residue in the "P-S-Y"-motif of its tail phosphorylated are completely refractory from being dispersed by Arc, suggesting that Arc cannot displace AMPARs from PSDs in active synapses. Conversely, strengthening the interaction between Arc and TARPs enhances Arc's capacity in weakening synapses. Thus, Arc can specifically and effectively modulate synaptic AMPAR clustering via modulating PSD phase separation. Our study further suggests that activity-dependent, bi-directional modulation of PSD condensate formation/dispersion represents a general regulatory mechanism for synaptic plasticity.
URL[Source Record]
Indexed By
Language
English
SUSTech Authorship
Corresponding
Funding Project
Minister of Science and Technology of China[2019YFA0508402] ; National Science Foundation of China[82188101] ; Research Grant Council of Hong Kong["AoE-M09-12","16104518","16101419"] ; HFSP Research Grant[RGP0020/2019] ; National Institute of Health[RO1 NS036715]
WOS Research Area
Cell Biology
WOS Subject
Cell Biology
WOS Accession No
WOS:000826806700002
Publisher
ESI Research Field
MOLECULAR BIOLOGY & GENETICS
Data Source
Web of Science
Citation statistics
Cited Times [WOS]:2
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/356167
DepartmentSchool of Life Sciences
Affiliation
1.Hong Kong Univ Sci & Technol, Div Life Sci, Kowloon, Clear Water Bay, Hong Kong, Peoples R China
2.Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
3.Johns Hopkins Univ, Sch Med, Kavli Neurosci Discovery Inst, Baltimore, MD 21205 USA
4.Southern Univ Sci & Technol, Sch Life Sci, Shenzhen, Guangdong, Peoples R China
Corresponding Author AffilicationSchool of Life Sciences
Recommended Citation
GB/T 7714
Chen, Xudong,Jia, Bowen,Araki, Yoichi,et al. Arc weakens synapses by dispersing AMPA receptors from postsynaptic density via modulating PSD phase separation[J]. CELL RESEARCH,2022.
APA
Chen, Xudong.,Jia, Bowen.,Araki, Yoichi.,Liu, Bian.,Ye, Fei.,...&Zhang, Mingjie.(2022).Arc weakens synapses by dispersing AMPA receptors from postsynaptic density via modulating PSD phase separation.CELL RESEARCH.
MLA
Chen, Xudong,et al."Arc weakens synapses by dispersing AMPA receptors from postsynaptic density via modulating PSD phase separation".CELL RESEARCH (2022).
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