Cited by 143Cellular transport and secretionNeuroscience and Neuropharmacology ResearchExtracellular vesicles in disease

Fusion Competent Synaptic Vesicles Persist upon Active Zone Disruption and Loss of Vesicle Docking

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Wang, Shan Shan H., Held, Richard G., Wong, Man Yan, Liu, Changliang, Karakhanyan, Aziz, Kaeser, Pascal S.·2016·Neuron

Abstract

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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Crossref · 10.1016/j.neuron.2016.07.005

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  1. Kittel RJ Wichmann C Rasse TM Fouquet W Schmidt M Schmid A Wagh DA Pawlu C Kellner RR Willig KI Bruchpilot promotes active zone assembly, Ca2+ channel clustering, and vesicle release Science 2006 312 1051 1054 (80-.). 16614170
  2. Ohtsuka T Takao-Rikitsu E Inoue E Inoue M Takeuchi M Matsubara K Deguchi-Tawarada M Satoh K Morimoto K Nakanishi H CAST: A novel protein of the cytomatrix at the active zone of synapses that forms a ternary complex with RIM1 and Munc13-1 J. Cell Biol 2002 158 577 590 12163476 PMC2173811

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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)
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
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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