Quantitative analysis of the native presynaptic cytomatrix by cryoelectron tomography
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The presynaptic terminal contains a complex network of filaments whose precise organization and functions are not yet understood. The cryoelectron tomography experiments reported in this study indicate that these structures play a prominent role in synaptic vesicle release. Docked synaptic vesicles did not make membrane to membrane contact with the active zone but were instead linked to it by tethers of different length. Our observations are consistent with an exocytosis model in which vesicles are first anchored by long (>5 nm) tethers that give way to multiple short tethers once vesicles enter the readily releasable pool. The formation of short tethers was inhibited by tetanus toxin, indicating that it depends on soluble N-ethyl-maleimide sensitive fusion protein attachment protein receptor complex assembly. Vesicles were extensively interlinked via a set of connectors that underwent profound rearrangements upon synaptic stimulation and okadaic acid treatment, suggesting a role of these connectors in synaptic vesicle mobilization and neurotransmitter release.
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In cryo-EM studies of unfixed and unstained synapse preparations, no dense projections are detectable; the only structures visible are the plasma membrane, synaptic vesicles, and sparse filaments that connect vesicles to each other or tether vesicles to the presynaptic plasma membrane.
“In cryo-EM studies of unfixed and unstained synapse preparations, however, no dense projections are detectable. The only structures visible are the plasma membrane, synaptic vesicles, and sparse filaments that either connect vesicles to each others (“connectors,” average length ~10 nm) or tether vesicles to the presynaptic plasma membrane (“tethers”—5–20 nm; Landis et al., 1988; Fernández-Busnadie”
From The Presynaptic Active Zone (2012) · cites this paper as Fernández-Busnadiego et al., 2010
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Experimental — accuracy not yet measuredActin filaments are excluded from the active zone and the vesicle cluster.
“Besides these proteins, actin was suggested to be an active zone component, but high-resolution electron microscopy (EM) shows that actin filaments are excluded from the active zone and the vesicle cluster (Fernández-Busnadiego et al., 2010).”
From The Presynaptic Active Zone (2012) · cites this paper as Fernández-Busnadiego et al., 2010
The Results (Morphology of frozen-hydrated presynaptic terminals; page unavailable) report that actin was only occasionally observed and that long actin bundles induced by OA treatment were generally more than 300 nm from the active zone. The Discussion (Synaptic vesicle distribution in resting synapses is not homogenous; page unavailable) cautions that very short or transient actin filaments could not be detected. The paper therefore supports a low abundance of detectable actin near the active zone, not categorical exclusion from both the active zone and vesicle cluster. (LLM, conf=0.86)
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- Authors
- Fernández-Busnadiego, R., Zuber, B., Maurer, U. E., Cyrklaff, M., Baumeister, W., & Lučić, V.
- Affiliations
- Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany 1
- MRC Laboratory of Molecular Biology (GB)
- Max Planck Institute of Biochemistry (DE)
- Corresponding author
- Baumeister, Wolfgang
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2010-01-11
- Volume
- 188
- Issue
- 1
- Pages
- 145-156
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2812849
- OpenAlex
- W2132214171
- Cited by
- 267
- References
- 66
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 21 · 2023: 18 · 2022: 15 · 2021: 14 · 2020: 16 · 2019: 13 · 2018: 16 · 2017: 18 · 2016: 13 · 2015: 17 · 2014: 17 · 2013: 14 · 2012: 16
- FWCI
- 8.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- 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
- synaptic vesicle release, docked vesicles, exocytosis, readily releasable pool, tetanus toxin, SNARE complex, okadaic acid, synaptic stimulation, neurotransmitter release, active zone, cryo-electron tomography
- MeSH terms
- Animals, Male, Synapses, Rats, Wistar, Tissue Culture Techniques, Rats, Electron Microscope Tomography
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