ArticleProceedings of the National Academy of Sciences of the United States of America2024
Thermodynamic modulation of gephyrin condensation by inhibitory synapse components.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Redox-dependent synaptic clustering of gephyrin.Nature communications · 2026Article
- Impaired gephyrin G-domain trimerization and phase separation in a patient with developmental epileptic encephalopathy.EMBO molecular medicine · 2026Article
- Cryo-EM structures of higher order Gephyrin oligomers reveal principles of inhibitory postsynaptic scaffold organization.Nature communications · 2026Article
- Competition between glycine and GABAProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Gephyrin filaments represent the molecular basis of inhibitory postsynaptic densities.Nature communications · 2025Article
- Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities.Molecular cancer · 2025Review
- Is the Activation of the Postsynaptic Ligand Gated Glycine- or GABABiomedicines · 2025Review
- Phosphoinositide- and Collybistin-Dependent Synaptic Clustering of Gephyrin.Journal of neurochemistry · 2025Article
- Enhancement of CEP215 dynamics for spindle pole assembly during mitosis.Journal of cell science · 2025Article
- Protein quality control machinery: regulators of condensate architecture and functionality.Trends in biochemical sciences · 2025Review
- Convergent evolution links molybdenum insertase domains with organism-specific sequences.Communications biology · 2024Article
Corrections and comments
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Authors and funding
9 authors.
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Abstract
Phase separation drives compartmentalization of intracellular contents into various biomolecular condensates. Individual condensate components are thought to differentially contribute to the organization and function of condensates. However, how intermolecular interactions among constituent biomolecules modulate the phase behaviors of multicomponent condensates remains unclear. Here, we used core components of the inhibitory postsynaptic density (iPSD) as a model system to quantitatively probe how the network of intra- and intermolecular interactions defines the composition and cellular distribution of biomolecular condensates. We found that oligomerization-driven phase separation of gephyrin, an iPSD-specific scaffold, is critically modulated by an intrinsically disordered linker region exhibiting minimal homotypic attractions. Other iPSD components, such as neurotransmitter receptors, differentially promote gephyrin condensation through distinct binding modes and affinities. We further demonstrated that the local accumulation of scaffold-binding proteins at the cell membrane promotes the nucleation of gephyrin condensates in neurons. These results suggest that in multicomponent systems, the extent of scaffold condensation can be fine-tuned by scaffold-binding factors, a potential regulatory mechanism for self-organized compartmentalization in cells.
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