Evidence map›Paper›PMID 35135883›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Munc13 structural transitions and oligomers that may choreograph successive stages in vesicle priming for neurotransmitter release.

Kirill Grushin, R Venkat Kalyana Sundaram, Charles V Sindelar, James E Rothman

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing 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

47 citing papers in PubMed.

  1. Article
  2. Article
  3. 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
  4. Article
  5. Synaptic transmission: Munc13 assembles onto PI(4,5)PProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Munc13-1 couples DAG and CaScience advances · 2026
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. PI(4,5)PBiochimica et biophysica acta. Molecular and cell biology of lipids · 2025
    Review
  14. Article
  15. A specific negatively charged sequence confers intramolecular regulation on Munc13-1 function in synaptic exocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Kirill GrushinDepartment of Cell Biology, Yale University, New Haven, CT 06520.
R Venkat Kalyana SundaramDepartment of Cell Biology, Yale University, New Haven, CT 06520.ORCID 0000-0002-0232-4186
Charles V SindelarDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520 james.rothman@yale.edu charles.sindelar@yale.edu.ORCID 0000-0002-6646-7776
James E RothmanDepartment of Cell Biology, Yale University, New Haven, CT 06520; james.rothman@yale.edu charles.sindelar@yale.edu.ORCID 0000-0003-4822-4161

Funding

Regulation of Membrane Fusion in ExocytosisR01DK027044 · NIDDK · YALE UNIVERSITY · PI KRISHNAKUMAR, SHYAM S · 1986 to 2021
$8.2M
MECHANISMS OF INTRACELLULAR MEMBRANE FUSIONR37DK027044 · NIDDK · YALE UNIVERSITY · PI ROTHMAN, JAMES · 1992 to 2012
$5.3M
Structural basis of motility by dimeric kinesin motor proteinsR01GM110530 · NIGMS · YALE UNIVERSITY · PI SINDELAR, CHARLES VAUGHN · 2014 to 2023
$3.0M
NIDDK NIH HHS R01 DK027044NIDDK NIH HHS R37 DK027044NIGMS NIH HHS R01 GM110530
6 · The paper itself

Abstract

How can exactly six SNARE complexes be assembled under each synaptic vesicle? Here we report cryo-EM crystal structures of the core domain of Munc13, the key chaperone that initiates SNAREpin assembly. The functional core of Munc13, consisting of C1-C2B-MUN-C2C (Munc13C) spontaneously crystallizes between phosphatidylserine-rich bilayers in two distinct conformations, each in a radically different oligomeric state. In the open conformation (state 1), Munc13C forms upright trimers that link the two bilayers, separating them by ∼21 nm. In the closed conformation, six copies of Munc13C interact to form a lateral hexamer elevated ∼14 nm above the bilayer. Open and closed conformations differ only by a rigid body rotation around a flexible hinge, which when performed cooperatively assembles Munc13 into a lateral hexamer (state 2) in which the key SNARE assembly-activating site of Munc13 is autoinhibited by its neighbor. We propose that each Munc13 in the lateral hexamer ultimately assembles a single SNAREpin, explaining how only and exactly six SNARE complexes are templated. We suggest that state 1 and state 2 may represent two successive states in the synaptic vesicle supply chain leading to "primed" ready-release vesicles in which SNAREpins are clamped and ready to release (state 3).

Indexed as

Gene Expression RegulationHEK293 CellsHumansModels, MolecularNerve Tissue ProteinsProtein ConformationNerve Tissue ProteinsUNC13B protein, humancryo-ETmembrane fusionMunc13SNAREsynaptic transmission

Identifiers

PMID35135883
PMCPMC8851502

What OpenQuestion holds

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LicenceCC BY-NC-ND
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 OpenQuestion graph.