Evidence map›Paper›PMID 26700321›Full record

ArticleMolecular biology of the cell2016

Conformational states of syntaxin-1 govern the necessity of N-peptide binding in exocytosis of PC12 cells and Caenorhabditis elegans.

Seungmee Park, Na-Ryum Bin, Maaran Rajah, Byungjin Kim, Ting-Chieh Chou, Soo-Young Ann Kang, Kyoko Sugita, Leon Parsaud, Matthew Smith, Philippe P Monnier and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular biology of the cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

11 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. SNARE Proteins in Synaptic Vesicle Fusion.Advances in neurobiology · 2023
    Article
  3. Review
  4. Article
  5. Article
  6. Chaperoning SNARE Folding and Assembly.Annual review of biochemistry · 2021
    Review
  7. Article
  8. Article
  9. The presynaptic machinery at the synapse of C. elegans.Invertebrate neuroscience : IN · 2018
    Review
  10. Article
  11. Review
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

13 authors at 2 institutions in 1 country.

Seungmee ParkDivision of Fundamental Neurobiology, University Health Network, Toronto, ON M5T 2S8, Canada Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Na-Ryum BinDivision of Fundamental Neurobiology, University Health Network, Toronto, ON M5T 2S8, Canada Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Maaran RajahDivision of Fundamental Neurobiology, University Health Network, Toronto, ON M5T 2S8, Canada.
Byungjin KimDivision of Fundamental Neurobiology, University Health Network, Toronto, ON M5T 2S8, Canada.
Ting-Chieh ChouDivision of Fundamental Neurobiology, University Health Network, Toronto, ON M5T 2S8, Canada Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Soo-Young Ann KangDivision of Fundamental Neurobiology, University Health Network, Toronto, ON M5T 2S8, Canada.
Kyoko SugitaDivision of Genetics and Development, Krembil Discovery Tower, University Health Network, Toronto, ON M5T 2S8, Canada.
Leon ParsaudDivision of Fundamental Neurobiology, University Health Network, Toronto, ON M5T 2S8, Canada Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Matthew SmithDivision of Signaling Biology, MaRS Toronto Medical Discovery Tower, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 1L7, Canada Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
Philippe P MonnierDepartment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada Division of Genetics and Development, Krembil Discovery Tower, University Health Network, Toronto, ON M5T 2S8, Canada.
Mitsuhiko IkuraDivision of Genetics and Development, Krembil Discovery Tower, University Health Network, Toronto, ON M5T 2S8, Canada Division of Signaling Biology, MaRS Toronto Medical Discovery Tower, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 1L7, Canada.
Mei ZhenLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Shuzo SugitaDivision of Fundamental Neurobiology, University Health Network, Toronto, ON M5T 2S8, Canada Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada ssugita@uhnres.utoronto.ca.
University Health Network · CAMount Sinai Hospital · CA

Funding

CIHR MOP-130573CIHR MOP-93665
6 · The paper itself

Abstract

Syntaxin-1 is the central SNARE protein for neuronal exocytosis. It interacts with Munc18-1 through its cytoplasmic domains, including the N-terminal peptide (N-peptide). Here we examine the role of the N-peptide binding in two conformational states ("closed" vs. "open") of syntaxin-1 using PC12 cells and Caenorhabditis elegans. We show that expression of "closed" syntaxin-1A carrying N-terminal single point mutations (D3R, L8A) that perturb interaction with the hydrophobic pocket of Munc18-1 rescues impaired secretion in syntaxin-1-depleted PC12 cells and the lethality and lethargy of unc-64 (C. elegans orthologue of syntaxin-1)-null mutants. Conversely, expression of the "open" syntaxin-1A harboring the same mutations fails to rescue the impairments. Biochemically, the L8A mutation alone slightly weakens the binding between "closed" syntaxin-1A and Munc18-1, whereas the same mutation in the "open" syntaxin-1A disrupts it. Our results reveal a striking interplay between the syntaxin-1 N-peptide and the conformational state of the protein. We propose that the N-peptide plays a critical role in intracellular trafficking of syntaxin-1, which is dependent on the conformational state of this protein. Surprisingly, however, the N-peptide binding mode seems dispensable for SNARE-mediated exocytosis per se, as long as the protein is trafficked to the plasma membrane.

Indexed as

ExocytosisAmino Acid SequenceAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsCell MembraneGene Knockdown TechniquesMolecular Sequence DataMunc18 ProteinsNeuronsPC12 CellsPeptidesPoint MutationProtein BindingProtein Structure, TertiaryProtein TransportCaenorhabditis elegans ProteinsMunc18 ProteinsPeptidesStx1a protein, ratStxbp1 protein, ratSyntaxin 1unc-64 protein, C elegans

Identifiers

PMID26700321
PMCPMC4750926
OpenAlexW2314275848

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.