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Cited by 61Cellular transport and secretionNeuroscience and Neuropharmacology ResearchCalcium signaling and nucleotide metabolism

CAPS-1 promotes fusion competence of stationary dense-core vesicles in presynaptic terminals of mammalian neurons

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Farina, Margherita, van de Bospoort, Rhea, He, Enqi, Persoon, Claudia M, van Weering, Jan RT, Broeke, Jurjen H, Verhage, Matthijs, Toonen, Ruud F·2015·eLife
DOI 10.7554/elife.05438PMC PMC4341531
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Abstract

Neuropeptides released from dense-core vesicles (DCVs) modulate neuronal activity, but the molecules driving DCV secretion in mammalian neurons are largely unknown. We studied the role of calcium-activator protein for secretion (CAPS) proteins in neuronal DCV secretion at single vesicle resolution. Endogenous CAPS-1 co-localized with synaptic markers but was not enriched at every synapse. Deletion of CAPS-1 and CAPS-2 did not affect DCV biogenesis, loading, transport or docking, but DCV secretion was reduced by 70% in CAPS-1/CAPS-2 double null mutant (DKO) neurons and remaining fusion events required prolonged stimulation. CAPS deletion specifically reduced secretion of stationary DCVs. CAPS-1-EYFP expression in DKO neurons restored DCV secretion, but CAPS-1-EYFP and DCVs rarely traveled together. Synaptic localization of CAPS-1-EYFP in DKO neurons was calcium dependent and DCV fusion probability correlated with synaptic CAPS-1-EYFP expression. These data indicate that CAPS-1 promotes fusion competence of immobile (tethered) DCVs in presynaptic terminals and that CAPS-1 localization to DCVs is probably not essential for this role.

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  • Enrichment in the curated gene list from the SPARK consortium was significant (P=0.0034).

    “while enrichment in the curated gene list from the SPARK consortium 80 was significant (P=0.0034).”

    From Identification of common genetic risk variants for autism spectrum disorder (2019) · cites this paper as [80]

    The Results passages concern CAPS-1 and dense-core vesicle release, while Materials and methods > Statistics describes tests used for those experiments; no page numbers are supplied. Searches for the SPARK consortium, curated gene-list enrichment, and P=0.0034 found no passage in our copy addressing the claimed result. (LLM, conf=0.76)

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Authors
Farina, M., van de Bospoort, R., He, E., Persoon, C. M., van Weering, J. R., Broeke, J. H., Verhage, M., & Toonen, R. F.
Affiliations
  • Vrije Universiteit Amsterdam (NL)
  • Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, Amsterdam, Netherlands
  • Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
  • Department of Clinical Genetics, VU University Medical Center, Amsterdam, Netherlands
Corresponding author
  • Verhage, Matthijs
  • Toonen, Ruud F
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2015-02-26
Volume
4
Pages
e12968-e12968
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.05438
PMC
PMC4341531
OpenAlex
W1979379929
Cited by
61
References
63
Citations by year
2025: 5 · 2024: 10 · 2023: 3 · 2022: 3 · 2021: 8 · 2020: 4 · 2019: 6 · 2018: 6 · 2017: 9 · 2016: 6 · 2015: 1
FWCI
3.90
Type
journal article
Language
en
Update notices
correction (2015-11-18)
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • VU Research Portal (publishedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
  • Netherlands Organisation for Health Research and Development (ZonMw) (916-66-101, 91208017, 90342095, 90001001)
  • Education, Audiovisual and Culture Executive Agency (EACEA) (Erasmus Mundus Joint Doctorate grant EU 2011-1632/001-001-EMJD)
  • European Research Council (ERC) (322966)
  • Sixth Framework Programme (EUSynapse 019055)
  • Seventh Framework Programme (HEALTH-F2-2009-241498, SynSys project HEALTH-F2-2009-242167)
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 › Physiology › Calcium signaling and nucleotide metabolism
Keywords
dense core vesicles, synaptic vesicle fusion, neuropeptide release, presynaptic terminals, vesicle tethering, vesicle biogenesis
MeSH terms
Animals, Calcium-Binding Proteins, Hippocampus, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Presynaptic Terminals, Mice

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