Evidence map›Paper›PMID 19812250›Full record

ArticleMolecular biology of the cell2009

Rescue of Munc18-1 and -2 double knockdown reveals the essential functions of interaction between Munc18 and closed syntaxin in PC12 cells.

Liping Han, Tiandan Jiang, Gayoung A Han, Nancy T Malintan, Li Xie, Li Wang, Frederick W Tse, Herbert Y Gaisano, Brett M Collins, Frederic A Meunier and 1 more

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

59 citing papers in PubMed, 88 citations in OpenAlex.

  1. Article
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  7. 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
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  8. Article
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  12. SNARE Proteins in Synaptic Vesicle Fusion.Advances in neurobiology · 2023
    Article
  13. Article
  14. Munc18-dependent and -independent clustering of syntaxin in the plasma membrane of cultured endocrine cells.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  15. Article
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  19. Review
  20. Structural and mechanistic insights into secretagogin-mediated exocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2020
    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

11 authors at 5 institutions in 3 countries.

Liping HanDivision of Fundamental Neurobiology, University Health Network, Toronto, Ontario, M5T 2S8, Canada.
Tiandan Jiang
Gayoung A Han
Nancy T Malintan
Li Xie
Li Wang
Frederick W Tse
Herbert Y Gaisano
Brett M Collins
Frederic A Meunier
Shuzo Sugita
University Health Network · CAAllen Institute for Brain Science · USThe University of Queensland · AUUniversity of Alberta · CAUniversity of Toronto · CA

Funding

Canadian Institutes of Health Research MOP-57825Canadian Institutes of Health Research MOP-64465
6 · The paper itself

Abstract

Munc18-1 binds to syntaxin-1A via two distinct sites referred to as the "closed" conformation and N terminus binding. The latter has been shown to stimulate soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated exocytosis, whereas the former is believed to be inhibitory or dispensable. To precisely define the contributions of each binding mode, we have engineered Munc18-1/-2 double knockdown neurosecretory cells and show that not only syntaxin-1A and -1B but also syntaxin-2 and -3 are significantly reduced as a result of Munc18-1 and -2 knockdown. Syntaxin-1 was mislocalized and the regulated secretion was abolished. We next examined the abilities of Munc18-1 mutants to rescue the defective phenotypes. Mutation (K46E/E59K) of Munc18-1 that selectively prevents binding to closed syntaxin-1 was unable to restore syntaxin-1 expression, localization, or secretion. In contrast, mutations (F115E/E132A) of Munc18-1 that selectively impair binding to the syntaxin-1 N terminus could still rescue the defective phenotypes. Our results indicate that Munc18-1 and -2 act in concert to support the expression of a broad range of syntaxins and to deliver syntaxin-1 to the plasma membrane. Our studies also indicate that the binding to the closed conformation of syntaxin is essential for Munc18-1 stimulatory action, whereas the binding to syntaxin N terminus plays a more limited role in neurosecretory cells.

Indexed as

Protein Structure, TertiaryAnimalsBinding SitesGene Knockdown TechniquesHumansModels, MolecularMunc18 ProteinsMutationPC12 CellsPhenotypeProtein BindingProteinsQa-SNARE ProteinsRatsRecombinant Fusion ProteinsSecretory VesiclesMunc18 Proteinsphospholipase A2-activating proteinProteinsQa-SNARE ProteinsRecombinant Fusion ProteinsStxbp1 protein, ratStxbp2 protein, rat

Identifiers

PMID19812250
PMCPMC2785739
OpenAlexW2083396869

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.