Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis
Open accessAbstract
It is currently unknown whether the molecular steps of large dense-core vesicle (LDCV) docking and priming are identical to the corresponding reactions in synaptic vesicle (SV) exocytosis. Munc13s are essential for SV docking and priming, and we systematically analyzed their role in LDCV exocytosis using chromaffin cells lacking individual isoforms. We show that particularly Munc13-2 plays a fundamental role in LDCV exocytosis, but in contrast to synapses lacking Munc13s, the corresponding chromaffin cells do not exhibit a vesicle docking defect. We further demonstrate that ubMunc13-2 and Munc13-1 confer Ca2+-dependent LDCV priming with similar affinities, but distinct kinetics. Using a mathematical model, we identify an early LDCV priming step that is strongly dependent upon Munc13s. Our data demonstrate that the molecular steps of SV and LDCV priming are very similar while SV and LDCV docking mechanisms are distinct.
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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 [15]
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Munc18-1 Promotes Large Dense-Core Vesicle Docking
Voets, T., Toonen, R. F., Brian, E. C., de Wit, H., Moser, T., Rettig, J., Südhof, T. C., Neher, E., & Verhage, M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00391-9 · Cited by 396 · cited 1× · see citing works
“Additionally, Munc18-1 docks LDCVs via its interaction with the closed form of Stx-1 (Gandasi and Barg, 2014; Gerber et al., 2008; Gulyas-Kovacs et al., 2007; Han et al., 2011; Voets et al., 2001) and is also involved in an additional tethering step (Toonen et al., 2006).”
BackgroundSelf-citationThe Morphological and Molecular Nature of Synaptic Vesicle Priming at Presynaptic Active Zones
Imig, C., Min, S.-W., Krinner, S., Arancillo, M., Rosenmund, C., Südhof, T. C., Rhee, J., Brose, N., & Cooper, B. H. (2014) · Neuron · doi:10.1016/j.neuron.2014.10.009 · Cited by 389 · see citing works
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- Authors
- Man, K. N. M., Imig, C., Walter, A. M., Pinheiro, P. S., Stevens, D. R., Rettig, J., Sørensen, J. B., Cooper, B. H., Brose, N., & Wojcik, S. M.
- Affiliations
- Max Planck Institute of Experimental Medicine (DE)
- Leibniz-Forschungsinstitut für Molekulare Pharmakologie (DE)
- University of Copenhagen (DK)
- Saarland University (DE)
- Corresponding author
- Wojcik, Sonja M
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2015-11-17
- Volume
- 4
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC4798968
- OpenAlex
- W2180854259
- Cited by
- 63
- References
- 5
- Citations by year
- 2025: 7 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 9 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 14 · 2016: 5 · 2015: 1 · 2014: 1
- FWCI
- 4.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
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- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
- GRO (submittedVersion, cc-by)
- Funders
- Max-Planck-Gesellschaft
- Deutsche Forschungsgemeinschaft
- 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, Munc13-1, large dense core vesicles, chromaffin cells, exocytosis, vesicle docking, vesicle priming, synaptic vesicles
- MeSH terms
- Animals, Exocytosis, Models, Biological, Nerve Tissue Proteins, Chromaffin Cells, Secretory Vesicles, Intracellular Signaling Peptides and Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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