Cited by 63Cellular transport and secretionNeuroscience and Neuropharmacology ResearchExtracellular vesicles in disease

Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis

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Man, Kwun Nok M, Imig, Cordelia, Walter, Alexander M, Pinheiro, Paulo S, Stevens, David R, Rettig, Jens, Sørensen, Jakob B, Cooper, Benjamin H +2 more·2015·eLife

Abstract

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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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
Venue
eLife
Published
2015-11-17
Volume
4
ISSN
2050-084X (ISSN-L)
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
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)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • 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

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