Fusion Competent Synaptic Vesicles Persist upon Active Zone Disruption and Loss of Vesicle Docking
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In a nerve terminal, synaptic vesicle docking and release are restricted to an active zone. The active zone is a protein scaffold that is attached to the presynaptic plasma membrane and opposed to postsynaptic receptors. Here, we generated conditional knockout mice removing the active zone proteins RIM and ELKS, which additionally led to loss of Munc13, Bassoon, Piccolo, and RIM-BP, indicating disassembly of the active zone. We observed a near-complete lack of synaptic vesicle docking and a strong reduction in vesicular release probability and the speed of exocytosis, but total vesicle numbers, SNARE protein levels, and postsynaptic densities remained unaffected. Despite loss of the priming proteins Munc13 and RIM and of docked vesicles, a pool of releasable vesicles remained. Thus, the active zone is necessary for synaptic vesicle docking and to enhance release probability, but releasable vesicles can be localized distant from the presynaptic plasma membrane.
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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 [16]
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- Authors
- Wang, S. S. H., Held, R. G., Wong, M. Y., Liu, C., Karakhanyan, A., & Kaeser, P. S.
- Affiliations
- Harvard University (US)
- Corresponding author
- Kaeser, Pascal S.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 91
- Issue
- 4
- Pages
- 777-791
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4991631
- OpenAlex
- W2513655066
- Cited by
- 143
- References
- 64
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 18 · 2023: 16 · 2022: 14 · 2021: 18 · 2020: 15 · 2019: 10 · 2018: 21 · 2017: 14 · 2016: 1 · 2015: 1 · 2014: 1
- FWCI
- 10.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (F31NS089077, P30NS072030, R01NS083898)
- 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, active zone, RIM, elk, Munc13, bassoon, piccolo, vesicle fusion, release probability, exocytosis, presynaptic terminals, conditional knockout mice, SNARE proteins, vesicle priming
- MeSH terms
- Animals, Carrier Proteins, Cells, Cultured, Cytoskeletal Proteins, Exocytosis, Membrane Fusion, Nerve Tissue Proteins, Neuropeptides, Synaptic Membranes, Synaptic Vesicles, Presynaptic Terminals, Mice, Knockout, ATP-Binding Cassette Transporters, rab GTP-Binding Proteins, SNARE Proteins, Mice, Post-Synaptic Density
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