Phase separation at the synapse
Abstract
Emerging evidence indicates that liquid-liquid phase separation, the formation of a condensed molecular assembly within another diluted aqueous solution, is a means for cells to organize highly condensed biological assemblies (also known as biological condensates or membraneless compartments) with very broad functions and regulatory properties in different subcellular regions. Molecular machineries dictating synaptic transmissions in both presynaptic boutons and postsynaptic densities of neuronal synapses may be such biological condensates. Here we review recent developments showing how phase separation can build dense synaptic molecular clusters, highlight unique features of such condensed clusters in the context of synaptic development and signaling, discuss how aberrant phase-separation-mediated synaptic assembly formation may contribute to dysfunctional signaling in psychiatric disorders, and present some challenges and opportunities of phase separation in synaptic biology.
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LLPS plays key roles in fundamental biological processes such as cytoskeletal regulation, synaptic signaling, and stress granule formation.
“In addition, LLPS plays key roles in fundamental biological processes such as cytoskeletal regulation, 26 synaptic signaling, 49 and stress granule formation. 50 , 51”
From Aberrant phase separation from a rare <i>ABI3</i> mutation drives microglial dysfunction and Alzheimer's risk (2026) · cites this paper as [49]
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- Authors
- Chen, X., Wu, X., Wu, H., & Zhang, M.
- Affiliations
- Hong Kong University of Science and Technology (HK)
- Corresponding author
- Zhang, Mingjie
- Venue
- Nature Neuroscience
- Published
- 2020-02-03
- Volume
- 23
- Issue
- 3
- Pages
- 301-310
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W3004042481
- Cited by
- 261
- References
- 15
- Citations by year
- 2026: 32 · 2025: 43 · 2024: 56 · 2023: 37 · 2022: 38 · 2021: 41 · 2020: 14
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- Research Grants Council, University Grants Committee (AoE-M09-12, C6004-17G)
- Simons Foundation (510178)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- liquid-liquid phase separation, biomolecular condensates, synaptic transmission, presynaptic terminals, postsynaptic density, synaptic development, synaptic signaling, mental illness
- MeSH terms
- Animals, Humans, Synaptic Transmission, Synapses, Presynaptic Terminals, Post-Synaptic Density
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