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The Morphological and Molecular Nature of Synaptic Vesicle Priming at Presynaptic Active Zones
Open accessAbstract
Synaptic vesicle docking, priming, and fusion at active zones are orchestrated by a complex molecular machinery. We employed hippocampal organotypic slice cultures from mice lacking key presynaptic proteins, cryofixation, and three-dimensional electron tomography to study the mechanism of synaptic vesicle docking in the same experimental setting, with high precision, and in a near-native state. We dissected previously indistinguishable, sequential steps in synaptic vesicle active zone recruitment (tethering) and membrane attachment (docking) and found that vesicle docking requires Munc13/CAPS family priming proteins and all three neuronal SNAREs, but not Synaptotagmin-1 or Complexins. Our data indicate that membrane-attached vesicles comprise the readily releasable pool of fusion-competent vesicles and that synaptic vesicle docking, priming, and trans-SNARE complex assembly are the respective morphological, functional, and molecular manifestations of the same process, which operates downstream of vesicle tethering by active zone components.
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“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 [14]
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“Furthermore, we discovered that forskolin slightly reduced the distance between CaV2.1 (P/Q-type) Ca2+ channels and Munc13-1, an essential vesicle priming protein and putative marker of primed vesicles [14,40–45].”
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 [14]
In the citing paper
“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 [14]
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Metadata
- Authors
- Imig, C., Min, S.-W., Krinner, S., Arancillo, M., Rosenmund, C., Südhof, T. C., Rhee, J., Brose, N., & Cooper, B. H.
- Affiliations
- Max Planck Institute of Experimental Medicine (DE)
- NeuroCure Cluster of Excellence (DE)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Brose, Nils
- Cooper, Benjamin H.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 84
- Issue
- 2
- Pages
- 416-431
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1996414800
- Cited by
- 389
- References
- 104
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 33 · 2023: 28 · 2022: 42 · 2021: 44 · 2020: 35 · 2019: 39 · 2018: 32 · 2017: 40 · 2016: 27 · 2015: 26 · 2014: 1
- FWCI
- 15.60
- Type
- journal article
- Language
- en
- Update notices
- erratum (2014-11-19)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- GRO (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- 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 priming, synaptic vesicle docking, active zone, Munc13, synaptotagmin-1, complexin, vesicle tethering, membrane adhesion, readily releasable pool, hippocampal synapses
- MeSH terms
- Animals, Hippocampus, Membrane Fusion, Synaptic Transmission, Neurons, Synapses, Synaptic Vesicles, SNARE Proteins, Mice
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