ArticleNature communications2021
PKC-phosphorylation of Liprin-α3 triggers phase separation and controls presynaptic active zone structure.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 104 citations in OpenAlex.
- Ternary Neurexin-T178-PTPR complexes represent a pre-synaptic core-module of neuronal synapse organization.Nature communications · 2026Article
- Liprin-α family proteins and their cellular functions.The Journal of biological chemistry · 2026Review
- Dissecting the propensity of RIM1 subdomains to form phase condensates.Scientific reports · 2026Article
- Article
- Physiological implications of phase separation in vesicle organization and trafficking.BMC biology · 2026Review
- Munc13 serves as a molecular filter for SNARE sorting and assembly in active zone condensates.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Sh3rf3 Deficiency drives autism-like behaviors via presynaptic dysfunction in mice.Molecular psychiatry · 2026Article
- Alzheimer's Pathology Enhances Excitatory Synaptic Input and Integration in VTA Dopamine Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Liquid-liquid phase separation in neural development.Cellular and molecular life sciences : CMLS · 2026Review
- Deployment of endocytic machinery to periactive zones of nerve terminals is independent of active zone assembly and evoked release.bioRxiv : the preprint server for biology · 2026Article
- A Scalable Design for Proximity-Inducing Molecules.bioRxiv : the preprint server for biology · 2026Article
- Spectrin condensates provide a nidus for assembling the axonal membrane-associated periodic skeleton.iScience · 2026Article
- Active Zone: Linking Resolution Levels of Microscopic Modalities.Advances in neurobiology · 2026Review
- Functional Nano-segregation of Distinct Forms of Neurotransmission.Advances in neurobiology · 2026Review
- Revealing acute consequences of rapid degradation of synaptic fusion proteins at individual synapses using Auxin-Inducible Degron 2 technology.Communications biology · 2025Article
- Synaptobrevin-2 disease variants reveal spatial constraints within the presynaptic active zone.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Submembrane liprin-α1 clusters spatially localize insulin granule fusion.The Journal of cell biology · 2025Article
- The synaptic vesicle cluster as a controller of pre- and postsynaptic structure and function.The Journal of physiology · 2025Review
- PKC-dependent enhancement of glutamate input to VTA dopamine neurons in 3xTg-AD mice.bioRxiv : the preprint server for biology · 2025Article
- Computer Simulations Show That Liquid-Liquid Phase Separation Enhances Self-Assembly.ACS nano · 2025Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The active zone of a presynaptic nerve terminal defines sites for neurotransmitter release. Its protein machinery may be organized through liquid-liquid phase separation, a mechanism for the formation of membrane-less subcellular compartments. Here, we show that the active zone protein Liprin-α3 rapidly and reversibly undergoes phase separation in transfected HEK293T cells. Condensate formation is triggered by Liprin-α3 PKC-phosphorylation at serine-760, and RIM and Munc13 are co-recruited into membrane-attached condensates. Phospho-specific antibodies establish phosphorylation of Liprin-α3 serine-760 in transfected cells and mouse brain tissue. In primary hippocampal neurons of newly generated Liprin-α2/α3 double knockout mice, synaptic levels of RIM and Munc13 are reduced and the pool of releasable vesicles is decreased. Re-expression of Liprin-α3 restored these presynaptic defects, while mutating the Liprin-α3 phosphorylation site to abolish phase condensation prevented this rescue. Finally, PKC activation in these neurons acutely increased RIM, Munc13 and neurotransmitter release, which depended on the presence of phosphorylatable Liprin-α3. Our findings indicate that PKC-mediated phosphorylation of Liprin-α3 triggers its phase separation and modulates active zone structure and function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.