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Cited by 50Cellular transport and secretionNeuroscience and Neuropharmacology ResearchExtracellular vesicles in disease

ELKS1 localizes the synaptic vesicle priming protein bMunc13-2 to a specific subset of active zones

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Kawabe, Hiroshi, Mitkovski, Miso, Kaeser, Pascal S., Hirrlinger, Johannes, Opazo, Felipe, Nestvogel, Dennis, Kalla, Stefan, Fejtova, Anna +12 more·2017·Journal of Cell Biology
DOI 10.1083/jcb.201606086PMC PMC5379939
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Abstract

Presynaptic active zones (AZs) are unique subcellular structures at neuronal synapses, which contain a network of specific proteins that control synaptic vesicle (SV) tethering, priming, and fusion. Munc13s are core AZ proteins with an essential function in SV priming. In hippocampal neurons, two different Munc13s—Munc13-1 and bMunc13-2—mediate opposite forms of presynaptic short-term plasticity and thus differentially affect neuronal network characteristics. We found that most presynapses of cortical and hippocampal neurons contain only Munc13-1, whereas ∼10% contain both Munc13-1 and bMunc13-2. Whereas the presynaptic recruitment and activation of Munc13-1 depends on Rab3-interacting proteins (RIMs), we demonstrate here that bMunc13-2 is recruited to synapses by the AZ protein ELKS1, but not ELKS2, and that this recruitment determines basal SV priming and short-term plasticity. Thus, synapse-specific interactions of different Munc13 isoforms with ELKS1 or RIMs are key determinants of the molecular and functional heterogeneity of presynaptic AZs.

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  • Forskolin changes only the localization of Munc13-1 but not bMunc13-2, which lacks C2A domain and is thought to prime vesicles independently of RIM.

    “In this context, it is interesting that forskolin changes only the localization of Munc13-1 but not bMunc13-2, which lacks C2A domain and is thought to prime vesicles independently of RIM [40,96].”

    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 [96]

    The Introduction (page unavailable) describes bMunc13-2 as having a distinct N terminus without the C2A/RIM-binding region and says proteins other than RIMs must be involved in its active-zone targeting and regulation. It does not establish that bMunc13-2 primes vesicles independently of RIM, and a search for forskolin found no passage reporting a differential effect on Munc13-1 and bMunc13-2 localization. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Authors
Kawabe, H., Mitkovski, M., Kaeser, P. S., Hirrlinger, J., Opazo, F., Nestvogel, D., Kalla, S., Fejtova, A., Verrier, S. E., Bungers, S. R., Cooper, B. H., Varoqueaux, F., Wang, Y., Nehring, R. B., Gundelfinger, E. D., Rosenmund, C., Rizzoli, S. O., Südhof, T. C., Rhee, J.-S., & Brose, N.
Affiliations
  • Max Planck Institute of Experimental Medicine (DE)
  • Light Microscopy Facility, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany 2
  • Howard Hughes Medical Institute (US)
  • Universitätsmedizin Göttingen (DE)
  • Department of Neurochemistry and Molecular Biology, Leibniz Institute of Neurobiology, 39118 Magdeburg, Germany 9
  • Max Planck Institute for Biophysical Chemistry (DE)
  • Department of Molecular Neurobiology, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany 1
  • The University of Texas Southwestern Medical Center (US)
  • Baylor College of Medicine (US)
  • Leibniz Institute for Neurobiology (DE)
  • NeuroCure Cluster of Excellence (DE)
Corresponding author
Brose, Nils
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2017-03-06
Volume
216
Issue
4
Pages
1143-1161
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.201606086
PMC
PMC5379939
OpenAlex
W2593794940
Cited by
50
References
12
Citations by year
2026: 1 · 2025: 7 · 2024: 1 · 2023: 4 · 2022: 12 · 2021: 6 · 2020: 2 · 2019: 2 · 2018: 6 · 2017: 8 · 2014: 1
FWCI
2.63
Type
journal article
Language
en
Update notices
correction (2017-03-13)
Open access
Licence
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by-nc-sa)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (DFG-CNMPB FZT103, SPP1365/KA3423/1-1, KA3423/3-1, SFB958/A5)
  • European Research Council
  • National Institutes of Health (NS051262, R01NS083898)
  • Fritz Thyssen Foundation
  • Japan Society for the Promotion of Science
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
Munc13-1, active zone, synaptic vesicle priming, RIM, short-term plasticity, synaptic vesicle fusion, hippocampal neurons, cortical neurons, synaptic vesicle tethering
MeSH terms
Animals, Cell Line, Hippocampus, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Synapses, Synaptic Vesicles, Protein Isoforms, rab3 GTP-Binding Proteins, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Mice

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