A common molecular basis for membrane docking and functional priming of synaptic vesicles
Open accessAbstract
Soluble N ‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) complexes execute synaptic vesicle (SV) fusion. Vesicle fusion is preceded by an obligatory Munc13‐dependent priming process that conveys fusion competence to SVs by facilitating SNARE complex assembly. Ultrastructural studies after chemical fixation indicated that vesicle docking to the plasma membrane is independent of Munc13s but these results may be misleading because aldehyde fixatives modify the localization of SVs with respect to the plasma membrane. To reinvestigate the role of Munc13s in vesicle docking, cultured hippocampal slices were immobilized using high‐pressure freezing, which circumvents aldehyde artifacts. High‐pressure freezing was combined with electron tomography to reach a resolution that allows the characterization of details of SV docking in a close‐to‐native state. In control slices, docked vesicles are not hemifused with the plasma membrane but linked to it and to dense material at the active zone by small strands. In slice cultures from Munc13‐deficient mice, vesicles are not docked to the active zone plasma membrane. These results indicate that SV docking at the plasma membrane and functional priming are respective morphological and physiological manifestations of the same molecular process mediated by SNARE complexes and Munc13s.
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In Munc13-1 KO mice synaptic vesicle docking appears to be normal as analyzed by EM of chemically fixed synapses but impaired as analyzed by cryo-EM of unfixed samples.
“For example, in Munc13-1 KO mice synaptic vesicle docking appears to be normal as analyzed by EM of chemically fixed synapses (Augustin et al., 1999) but impaired as analyzed by cryo-EM of unfixed samples (Siksou et al., 2009).”
From The Presynaptic Active Zone (2012) · cites this paper as Siksou et al., 2009
The Introduction describes high-pressure freezing combined with electron tomography, and the Results report an almost complete loss of docked vesicles. But the mice studied were Munc13-1/2 double knockouts, not the Munc13-1 knockouts named in the citing sentence. The chemical-fixation finding is attached to a different citation. (LLM, conf=0.90)
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Self-citationFusion Competent Synaptic Vesicles Persist upon Active Zone Disruption and Loss of Vesicle Docking
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- Authors
- Siksou, L., Varoqueaux, F., Pascual, O., Triller, A., Brose, N., & Marty, S.
- Affiliations
- Inserm (FR)
- Max Planck Society (DE)
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2009-06-29
- Volume
- 30
- Issue
- 1
- Pages
- 49-56
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2064268683
- Cited by
- 160
- References
- 3
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 4 · 2023: 10 · 2022: 9 · 2021: 10 · 2020: 7 · 2019: 10 · 2018: 6 · 2017: 12 · 2016: 13 · 2015: 12 · 2014: 9 · 2013: 13 · 2012: 8
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- GRO (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale
- Max-Planck-Gesellschaft
- Centre National de la Recherche Scientifique
- Fédération pour la Recherche sur le Cerveau
- 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
- synaptic vesicle docking, synaptic vesicle priming, Munc13, SNARE complex, vesicle fusion, active zone, high-pressure freezing, electron tomography, hippocampal slices, neurotransmitter release
- MeSH terms
- Animals, Cell Membrane, Cytoskeletal Proteins, Freezing, Hippocampus, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Pressure, Synapses, Synaptic Vesicles, Presynaptic Terminals, Mice, Knockout, Patch-Clamp Techniques, Imaging, Three-Dimensional, Intracellular Signaling Peptides and Proteins, Mice, Electron Microscope Tomography, In Vitro Techniques
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