Munc13 supports fusogenicity of non-docked vesicles at synapses with disrupted active zones.
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Abstract
Active zones consist of protein scaffolds that are tightly attached to the presynaptic plasma membrane. They dock and prime synaptic vesicles, couple them to voltage-gated Ca 2+ channels, and direct neurotransmitter release toward postsynaptic receptor domains. Simultaneous RIM + ELKS ablation disrupts these scaffolds, abolishes vesicle docking, and removes active zone-targeted Munc13, but some vesicles remain releasable. To assess whether this enduring vesicular fusogenicity is mediated by non-active zone-anchored Munc13 or is Munc13-independent, we ablated Munc13-1 and Munc13-2 in addition to RIM + ELKS in mouse hippocampal neurons. The hextuple knockout synapses lacked docked vesicles, but other ultrastructural features were near-normal despite the strong genetic manipulation. Removing Munc13 in addition to RIM + ELKS impaired action potential-evoked vesicle fusion more strongly than RIM + ELKS knockout by further decreasing the releasable vesicle pool. Hence, Munc13 can support some fusogenicity without RIM and ELKS, and presynaptic recruitment of Munc13, even without active zone anchoring, suffices to generate some fusion-competent vesicles.
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The readily releasable pool often closely correlates with the pool of docked vesicles, but exceptions to this correlation have been observed.
“For example, the readily releasable pool (RRP) often closely correlates with the pool of docked vesicles (i.e., vesicles in the direct contact with AZ plasma membrane) [14] but exceptions to this correlation have been also observed [15–17].”
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 [17]
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- Authors
- Tan, C., de Nola, G., Qiao, C., Imig, C., Born, R. T., Brose, N., & Kaeser, P. S.
- Affiliations
- Harvard University (US)
- Department of Neurobiology, Harvard Medical School
- University of Copenhagen (DK)
- Max Planck Society (DE)
- Corresponding author
- Kaeser, Pascal S
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2022-11-18
- Volume
- 11
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC9822248
- OpenAlex
- W4309361073
- Cited by
- 17
- References
- 65
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 3 · 2022: 1
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Funders
- National Institute of Mental Health (MH113349)
- National Institute of Neurological Disorders and Stroke (NS083898)
- Harvard Medical School
- Max Planck Institute for Multidisciplinary Sciences (open access funding)
- German Research Foundation (EXC 2067/1-390729940)
- 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 › Molecular Biology › Extracellular vesicles in disease
- Keywords
- Munc13, vesicle fusion, synaptic vesicle docking, active zone, RIM, elk, neurotransmitter release, Munc13-1, hippocampal neurons, synaptic ultrastructure
- MeSH terms
- Animals, Carrier Proteins, Synaptic Transmission, Neurons, Synapses, Synaptic Vesicles, Presynaptic Terminals, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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