Evidence map›Paper›PMID 23665562›Full record

ArticleThe Journal of biological chemistry2013

Synip arrests soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent membrane fusion as a selective target membrane SNARE-binding inhibitor.

Haijia Yu, Shailendra S Rathore, Jingshi Shen

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 20% 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

17 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Controlling of glutamate release by neuregulin3 via inhibiting the assembly of the SNARE complex.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  8. RABIF/MSS4 is a Rab-stabilizing holdase chaperone required for GLUT4 exocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Munc18c: a controversial regulator of peripheral insulin action.Trends in endocrinology and metabolism: TEM · 2014
    Review
  16. Article
  17. Comparative studies of Munc18c and Munc18-1 reveal conserved and divergent mechanisms of Sec1/Munc18 proteins.Proceedings of the National Academy of Sciences of the United States of America · 2013
    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

3 authors at 1 institution in 1 country.

Haijia YuDepartment of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.
Shailendra S Rathore
Jingshi Shen
University of Colorado Boulder · US

Funding

Regulatory Mechanisms of GLUT4 ExocytosisR01DK095367 · NIDDK · UNIVERSITY OF COLORADO · PI SHEN, JINGSHI · 2013 to 2017
$1.7M
Protein-Membrane Interactions in Regulated ExocytosisR01GM102217 · NIGMS · UNIVERSITY OF COLORADO · PI SHEN, JINGSHI · 2013 to 2017
$1.5M
Regulation of GLUT4 ExocytosisR00DK080080 · NIDDK · UNIVERSITY OF COLORADO · PI SHEN, JINGSHI · 2009 to 2011
$779k
Regulatory Mechanisms of GLUT4 ExocytosisR56DK095367 · NIDDK · UNIVERSITY OF COLORADO · PI SHEN, JINGSHI · 2012 to 2018
$598k
Regulation of GLUT4 ExocytosisK99DK080080 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SHEN, JINGSHI · 2007 to 2008
$181k
NIDDK NIH HHS DK080080NIDDK NIH HHS DK095367NIDDK NIH HHS K99 DK080080NIDDK NIH HHS R00 DK080080NIDDK NIH HHS R01 DK095367NIDDK NIH HHS R56 DK095367NIGMS NIH HHS R01 GM102217
6 · The paper itself

Abstract

The vesicle fusion reaction in regulated exocytosis requires the concerted action of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) core fusion engine and a group of SNARE-binding regulatory factors. The regulatory mechanisms of vesicle fusion remain poorly understood in most exocytic pathways. Here, we reconstituted the SNARE-dependent vesicle fusion reaction of GLUT4 exocytosis in vitro using purified components. Using this defined fusion system, we discovered that the regulatory factor synip binds to GLUT4 exocytic SNAREs and inhibits the docking, lipid mixing, and content mixing of the fusion reaction. Synip arrests fusion by binding the target membrane SNARE (t-SNARE) complex and preventing the initiation of ternary SNARE complex assembly. Although synip also interacts with the syntaxin-4 monomer, it does not inhibit the pairing of syntaxin-4 with SNAP-23. Interestingly, synip selectively arrests the fusion reactions reconstituted with its cognate SNAREs, suggesting that the defined system recapitulates the biological functions of the vesicle fusion proteins. We further showed that the inhibitory function of synip is dominant over the stimulatory activity of Sec1/Munc18 proteins. Importantly, the inhibitory function of synip is distinct from how other fusion inhibitors arrest SNARE-dependent membrane fusion and therefore likely represents a novel regulatory mechanism of vesicle fusion.

Indexed as

AnimalsCell MembraneExocytosisGlucose Transporter Type 4InsectaLipid BilayersLiposomesMembrane FusionMiceMunc18 ProteinsProtein BindingQa-SNARE ProteinsRecombinant ProteinsSNARE ProteinsVesicular Transport ProteinsGlucose Transporter Type 4Lipid BilayersLiposomesMunc18 ProteinsQa-SNARE ProteinsRecombinant ProteinsSlc2a4 protein, mouseSNARE ProteinsStxbp4 protein, mouseVesicular Transport ProteinsMembrane FusionMembrane ProteinsMembrane ReconstitutionMembrane TraffickingVesicles

Identifiers

PMID23665562
PMCPMC3696664
OpenAlexW2142952771

What OpenQuestion holds

Textmetadata
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.