Munc13 structural transitions and oligomers that may choreograph successive stages in vesicle priming for neurotransmitter release
Open accessAbstract
Significance: The speed of neural information processing in the human central nervous system is ultimately determined by the speed of chemical transmission at synapses, because action potentials have relatively short distances to traverse. The release of synaptic vesicles containing neurotransmitters must therefore be remarkably fast as compared to other forms of membrane fusion. Six separate SNARE complexes cooperate to achieve this. But how can exactly six copies be assembled under every vesicle? Here we report that six copies of the key molecular chaperone that assembles the SNAREs can arrange themselves into a closed hexagon, providing the likely answer.
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Munc13-1/2 are putative markers of primed vesicles.
“and Munc13-1/2, putative markers of primed vesicles [14,42–45,60,61].”
From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [61]
The Results section identifies the protein studied as a portion of Munc13-1 and says its C2C domain is required for synaptic-vesicle priming. The Discussion’s three-state model also places Munc13 on vesicles before they are primed. These passages support a role for Munc13-1 in priming, but do not establish Munc13-1/2 as markers of primed vesicles; the paper does not address Munc13-2. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThe corresponding active zone membrane association can be detected by freeze-fracture replica labeling.
“The corresponding AZ membrane association can be detected by FRL [23,61,66,67].”
From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [61]
The Results section describes Munc13C associated with model membrane bilayers using cryo-electron tomography. The supplied passages and searches for “FRL” and “freeze-fracture replica labeling” found no passage addressing whether active-zone membrane association can be detected by that method. (LLM, conf=0.72)
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- Authors
- Grushin, K., Kalyana Sundaram, R. V., Sindelar, C. V., & Rothman, J. E.
- Affiliations
- Yale University (US)
- Department of Cell Biology, Yale University, New Haven, CT 06520
- Corresponding author
- Sindelar, Charles V.
- Rothman, James E.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2022-02-08
- Volume
- 119
- Issue
- 7
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC8851502
- OpenAlex
- W4210927784
- Cited by
- 66
- References
- 78
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 11 · 2023: 15 · 2022: 13
- FWCI
- 7.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- HHS | National Institutes of Health (DK 027044, GM 110530)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Keywords
- Munc13, SNARE complex assembly, synaptic vesicle priming, neurotransmitter release, oligomeric state, conformational change, autoinhibition, synaptic vesicle fusion
- MeSH terms
- Gene Expression Regulation, Humans, Models, Molecular, Nerve Tissue Proteins, Protein Conformation, HEK293 Cells
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