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Updated: Sep 4, 2025
10:34
A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
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Arc weakens synapses by dispersing AMPA receptors from postsynaptic density via modulating PSD phase separation
Xudong Chen1, Bowen Jia1, Yoichi Araki2
1Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Cell Research
|July 20, 2022
Summary
The immediate early gene product Arc removes AMPA receptors (AMPARs) from synapses, regulating synaptic plasticity. This study reveals Arc disperses TARPs from postsynaptic density condensates, controlling AMPAR clustering and synaptic strength.
Area of Science:
- Neuroscience
- Molecular Biology
- Synaptic Plasticity
Background:
- The immediate early gene product Arc regulates synaptic plasticity by removing AMPA receptors (AMPARs) from synapses.
- The precise mechanism by which Arc facilitates AMPAR removal remains unclear.
Purpose of the Study:
- To elucidate the molecular mechanism by which Arc specifically mediates the removal of AMPARs from synapses.
- To investigate the role of TARPs and postsynaptic density (PSD) phase separation in Arc-mediated synaptic modulation.
Main Methods:
- Investigated the interaction between Arc and TARPs (auxiliary AMPAR subunits).
- Examined the effect of Arc on TARP localization within PSD condensates.
- Assessed the impact of TARP phosphorylation on Arc-mediated dispersal.
- Studied the relationship between Arc-TARP interaction strength and synaptic weakening.
Main Results:
- Arc directly antagonizes PSD-95 binding to TARPs.
- Arc disperses TARPs from PSD condensates in a concentration-dependent manner.
- Phosphorylation of TARPs prevents their dispersal by Arc, indicating Arc cannot displace AMPARs from active synapses.
- Enhanced Arc-TARP interaction strengthens Arc's capacity to weaken synapses.
Conclusions:
- Arc modulates synaptic AMPAR clustering by regulating PSD phase separation.
- Activity-dependent modulation of PSD condensate formation/dispersion is a general mechanism for synaptic plasticity.
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