Reconstituted Postsynaptic Density as a Molecular Platform for Understanding Synapse Formation and Plasticity
Open accessAbstract
Synapses are semi-membraneless, protein-dense, sub-micron chemical reaction compartments responsible for signal processing in each and every neuron. Proper formation and dynamic responses to stimulations of synapses, both during development and in adult, are fundamental to functions of mammalian brains, although the molecular basis governing formation and modulation of compartmentalized synaptic assemblies is unclear. Here, we used a biochemical reconstitution approach to show that, both in solution and on supported membrane bilayers, multivalent interaction networks formed by major excitatory postsynaptic density (PSD) scaffold proteins led to formation of PSD-like assemblies via phase separation. The reconstituted PSD-like assemblies can cluster receptors, selectively concentrate enzymes, promote actin bundle formation, and expel inhibitory postsynaptic proteins. Additionally, the condensed phase PSD assemblies have features that are distinct from those in homogeneous solutions and fit for synaptic functions. Thus, we have built a molecular platform for understanding how neuronal synapses are formed and dynamically regulated.
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LLPS may be a general mechanism for assembly of PSDs, and changes in protein expression or phosphorylation can effect a desired change in synaptic strength via modulation of phase separation in the PSD.
“As we explore mechanisms for recruiting AMPARs to the synapse it will be important to consider that LLPS may be a general mechanism for assembly of PSDs and that changes in protein expression or phosphorylation can effect a desired change in synaptic strength via modulation of phase separation in the PSD (301).”
From Synaptic memory and CaMKII (2023) · cites this paper as [301]
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- Authors
- Zeng, M., Chen, X., Guan, D., Xu, J., Wu, H., Tong, P., & Zhang, M.
- Affiliations
- Hong Kong University of Science and Technology (HK)
- Corresponding author
- Zhang, Mingjie
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 174
- Issue
- 5
- Pages
- 1172-1187.e16
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2886239953
- Cited by
- 438
- References
- 8
- Citations by year
- 2026: 38 · 2025: 71 · 2024: 58 · 2023: 51 · 2022: 70 · 2021: 70 · 2020: 40 · 2019: 37 · 2018: 2 · 2014: 1
- FWCI
- 17.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- Research Grants Council, University Grants Committee (C6004-17G, AoE-M09-12, C6004-14G, AoE/P-02/12)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- postsynaptic density, synaptogenesis, synaptic plasticity, biochemical reconstitution, phase separation, multivalent protein interactions, receptor clustering, enzyme concentration
- MeSH terms
- Disks Large Homolog 4 Protein, Animals, Brain, Hippocampus, Light, Synaptic Transmission, Neuronal Plasticity, Neurons, Scattering, Radiation, Synapses, Signal Transduction, Microscopy, Confocal, Mice, Neurogenesis, Post-Synaptic Density
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