Cited by 27Neuroscience and Neuropharmacology ResearchCellular transport and secretionIon channel regulation and function

Distinct active zone protein machineries mediate Ca2+ channel clustering and vesicle priming at hippocampal synapses

Open access
Emperador-Melero, Javier, Andersen, Jonathan W., Metzbower, Sarah R., Levy, Aaron D., Dharmasri, Poorna A., de Nola, Giovanni, Blanpied, Thomas A., Kaeser, Pascal S.·2024·Nature Neuroscience

Abstract

Action potentials trigger neurotransmitter release at the presynaptic active zone with spatiotemporal precision. This is supported by protein machinery that mediates synaptic vesicle priming and clustering of Ca V 2 Ca 2+ channels nearby. One model posits that scaffolding proteins directly tether vesicles to Ca V 2s; however, here we find that at mouse hippocampal synapses, Ca V 2 clustering and vesicle priming are executed by separate machineries. Ca V 2 nanoclusters are positioned at variable distances from those of the priming protein Munc13. The active zone organizer RIM anchors both proteins but distinct interaction motifs independently execute these functions. In transfected cells, Liprin-α and RIM form co-assemblies that are separate from Ca V 2-organizing complexes. At synapses, Liprin-α1-Liprin-α4 knockout impairs vesicle priming but not Ca V 2 clustering. The cell adhesion protein PTPσ recruits Liprin-α, RIM and Munc13 into priming complexes without co-clustering Ca V 2s. We conclude that active zones consist of distinct machineries to organize Ca V 2s and prime vesicles, and Liprin-α and PTPσ specifically support priming site assembly.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41593-024-01720-5

Cites

89 of 89 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 1

  1. [12]Kittel RJ Bruchpilot promotes active zone assembly, Ca2+ channel clustering, and vesicle release. Science 312, 1051– 4 (2006). 16614170

Cited by

Sorted by citations

Authors
Emperador-Melero, J., Andersen, J. W., Metzbower, S. R., Levy, A. D., Dharmasri, P. A., de Nola, G., Blanpied, T. A., & Kaeser, P. S.
Affiliations
  • Harvard University (US)
  • University of Maryland, Baltimore (US)
Corresponding author
Kaeser, Pascal S.
Venue
Nature Neuroscience
Published
2024-08-19
Volume
27
Issue
9
Pages
1680-1694
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W4401685161
Cited by
27
References
89
Citations by year
2026: 8 · 2025: 15 · 2024: 3 · 2023: 1
FWCI
4.55
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (R01NS083898, K99NS129959)
  • U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (R01MH113349, F31MH117920, R37MH080046)
  • Harvard Medical School (NA)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
active zone, synaptic vesicle priming, Munc13, RIM, Liprin-α, PTPσ, hippocampal synapses, neurotransmitter release
MeSH terms
Animals, Hippocampus, Mice, Inbred C57BL, Nerve Tissue Proteins, Synapses, Synaptic Vesicles, Calcium Channels, Mice, Knockout, Caveolin 2, 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 ›

Are you an author, or do you see a problem with this page? Request a review