Evidence map›Paper›PMID 38923992›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2024

Nanoscale architecture of synaptic vesicles and scaffolding complexes revealed by cryo-electron tomography.

Richard G Held, Jiahao Liang, Axel T Brunger

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Transsynaptic linking of calcium channels and postsynaptic receptors at a dyadic synapse.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Munc13 serves as a molecular filter for SNARE sorting and assembly in active zone condensates.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Article
  7. Review
  8. Synaptic transmission: Munc13 assembles onto PI(4,5)PProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Synaptobrevin-2 disease variants reveal spatial constraints within the presynaptic active zone.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors.

Richard G HeldDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.ORCID 0000-0001-8231-0341
Jiahao LiangDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.ORCID 0000-0002-6701-4808
Axel T BrungerDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.ORCID 0000-0001-5121-2036

Funding

The Stanford-SLAC CryoEM Center supplementU24GM129541 · NIGMS · STANFORD UNIVERSITY · PI CHIU, WAH, HEDMAN, BRITT · 2018 to 2023
$54.8M
Stanford-SLAC CryoET Specimen Preparation Service Center (SCSC) SupplementU24GM139166 · NIGMS · STANFORD UNIVERSITY · PI Wah Chiu · 2020 to 2026
$11.7M
STRUCTURE OF PROTEINS INVOLVED IN SYNAPTIC EXOCYTOSISR01MH063105 · NIMH · STANFORD UNIVERSITY · PI BRUNGER, AXEL T · 2000 to 2025
$4.7M
Single molecule studies of SNARE-induced vesicle fusionR37MH063105 · NIMH · STANFORD UNIVERSITY · PI BRUNGER, AXEL T · 2011 to 2020
$4.7M
Foundation for the National Institutes of Health (FNIH) MH063105Howard Hughes Medical Institute (HHMI) N/ANIGMS NIH HHS U24 GM129541NIGMS NIH HHS U24 GM139166NIMH NIH HHS R01 MH063105NIMH NIH HHS R37 MH063105
6 · The paper itself

Abstract

The spatial distribution of proteins and their arrangement within the cellular ultrastructure regulates the opening of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in response to glutamate release at the synapse. Fluorescence microscopy imaging revealed that the postsynaptic density (PSD) and scaffolding proteins in the presynaptic active zone (AZ) align across the synapse to form a trans-synaptic "nanocolumn," but the relation to synaptic vesicle release sites is uncertain. Here, we employ focused-ion beam (FIB) milling and cryoelectron tomography to image synapses under near-native conditions. Improved image contrast, enabled by FIB milling, allows simultaneous visualization of supramolecular nanoclusters within the AZ and PSD and synaptic vesicles. Surprisingly, membrane-proximal synaptic vesicles, which fuse to release glutamate, are not preferentially aligned with AZ or PSD nanoclusters. These synaptic vesicles are linked to the membrane by peripheral protein densities, often consistent in size and shape with Munc13, as well as globular densities bridging the synaptic vesicle and plasma membrane, consistent with prefusion complexes of SNAREs, synaptotagmins, and complexin. Monte Carlo simulations of synaptic transmission events using biorealistic models guided by our tomograms predict that clustering AMPARs within PSD nanoclusters increases the variability of the postsynaptic response but not its average amplitude. Together, our data support a model in which synaptic strength is tuned at the level of single vesicles by the spatial relationship between scaffolding nanoclusters and single synaptic vesicle fusion sites.

Indexed as

Electron Microscope TomographySynaptic VesiclesAnimalsCryoelectron MicroscopyPost-Synaptic DensityRatsSynapsescryo-electron tomographynanoscale topographysynapsesynaptic transmission

Identifiers

PMID38923992
PMCPMC11228483

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.