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Munc13 serves as a molecular filter for SNARE sorting and assembly in active zone condensates
Hong Zhang1, Yu Zhang1, Zhifei Zhao1
1Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Provincial Research Center for Basic Biological Sciences, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
Summary
Munc13-1 organizes SNARE proteins within RIM1/RIM-BP2 condensates, enhancing neurotransmitter release. This process concentrates SNAREs for precise and rapid synaptic vesicle exocytosis.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Neurotransmitter release relies on SNARE machinery assembly at presynaptic sites.
- Liquid-liquid phase separation organizes active zones, but SNARE enrichment mechanisms are unclear.
Purpose of the Study:
- To elucidate the mechanism of SNARE machinery enrichment within active zone scaffolds.
- To understand the role of Munc13-1 in organizing SNAREs within biomolecular condensates.
Main Methods:
- Investigated Munc13-1 function in RIM1/RIM-BP2 biomolecular condensates.
- Analyzed SNARE clustering and assembly within these condensates.
- Utilized PC12 cells to study dense-core vesicle exocytosis.
Main Results:
- Munc13-1 acts as a hub, spatially sorting and concentrating SNAREs within RIM1/RIM-BP2 condensates.
- Munc13-1 clusters Synaptobrevin 2 (Syb2) into nanodomains, increasing local SNARE density.
- RIM1/RIM-BP2 expression enhances precise dense-core vesicle exocytosis in a Munc13-dependent manner.
Conclusions:
- Phase separation provides a platform for Munc13-1 to direct SNARE complex assembly.
- This mechanism ensures the speed and precision of synaptic vesicle exocytosis.
- Munc13-1 is crucial for organizing the SNARE machinery for efficient neurotransmission.
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