Evidence map›Paper›PMID 30700546›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

SNARE machinery is optimized for ultrafast fusion.

Fabio Manca, Frederic Pincet, Lev Truskinovsky, James E Rothman, Lionel Foret, Matthieu Caruel

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.7field-weighted citation impact, top 11% of its field
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

31 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Article
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  7. Article
  8. Mechanisms of SNARE proteins in membrane fusion.Nature reviews. Molecular cell biology · 2024
    Review
  9. Synaptophysin chaperones the assembly of 12 SNAREpins under each ready-release vesicle.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  10. Article
  11. Roles for diacylglycerol in synaptic vesicle priming and release revealed by complete reconstitution of core protein machinery.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  12. Article
  13. Article
  14. CHARMM-GUIJournal of chemical theory and computation · 2023
    Review
  15. SNARE Proteins in Synaptic Vesicle Fusion.Advances in neurobiology · 2023
    Article
  16. Review
  17. Article
  18. Energetics, kinetics, and pathways of SNARE assembly in membrane fusion.Critical reviews in biochemistry and molecular biology · 2022
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 3 countries.

Fabio MancaLaboratoire de Physique de l'Ecole Normale Supérieure (LPENS), CNRS, Ecole Normale Supérieure, 75005 Paris, France.
Frederic PincetLaboratoire de Physique de l'Ecole Normale Supérieure (LPENS), CNRS, Ecole Normale Supérieure, 75005 Paris, France.
Lev TruskinovskyPhysique et Mécanique des Milieux Hétérogènes, CNRS, Ecole Supérieure de Physique et de Chimie Industrielles, Université PSL, 75231 Paris Cedex 05, France.
James E RothmanDepartment of Cell Biology, Yale University, New Haven, CT 06520; james.rothman@yale.edu matthieu.caruel@u-pec.fr.
Lionel ForetLaboratoire de Physique de l'Ecole Normale Supérieure (LPENS), CNRS, Ecole Normale Supérieure, 75005 Paris, France.
Matthieu CaruelModélisation et Simulation Multi-Echelle, CNRS, Université Paris-Est Créteil, 94010 Créteil Cedex, France james.rothman@yale.edu matthieu.caruel@u-pec.fr.ORCID 0000-0002-6591-2727
Centre National de la Recherche Scientifique · FRYale University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

SNARE proteins zipper to form complexes (SNAREpins) that power vesicle fusion with target membranes in a variety of biological processes. A single SNAREpin takes about 1 s to fuse two bilayers, yet a handful can ensure release of neurotransmitters from synaptic vesicles much faster: in a 10th of a millisecond. We propose that, similar to the case of muscle myosins, the ultrafast fusion results from cooperative action of many SNAREpins. The coupling originates from mechanical interactions induced by confining scaffolds. Each SNAREpin is known to have enough energy to overcome the fusion barrier of 25-[Formula: see text]; however, the fusion barrier only becomes relevant when the SNAREpins are nearly completely zippered, and from this state, each SNAREpin can deliver only a small fraction of this energy as mechanical work. Therefore, they have to act cooperatively, and we show that at least three of them are needed to ensure fusion in less than a millisecond. However, to reach the prefusion state collectively, starting from the experimentally observed half-zippered metastable state, the SNAREpins have to mechanically synchronize, which takes more time as the number of SNAREpins increases. Incorporating this somewhat counterintuitive idea in a simple coarse-grained model results in the prediction that there should be an optimum number of SNAREpins for submillisecond fusion: three to six over a wide range of parameters. Interestingly, in situ cryoelectron microscope tomography has very recently shown that exactly six SNAREpins participate in the fusion of each synaptic vesicle. This number is in the range predicted by our theory.

Indexed as

AnimalsCryoelectron MicroscopyMembrane FusionModels, BiologicalProtein BindingSNARE ProteinsSNARE Proteinsmembrane fusionmuscle contractionneurotransmitter releaseprotein foldingSNARE

Identifiers

PMID30700546
PMCPMC6377469
OpenAlexW2915058665

What OpenQuestion holds

Textmetadata
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.