Evidence map›Paper›PMID 27402227›Full record

ArticleThe EMBO journal2016

Phosphorylation of residues inside the SNARE complex suppresses secretory vesicle fusion.

Seth Malmersjö, Serena Di Palma, Jiajie Diao, Ying Lai, Richard A Pfuetzner, Austin L Wang, Moira A McMahon, Arnold Hayer, Matthew Porteus, Bernd Bodenmiller and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.3field-weighted citation impact, top 14% 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

27 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
  2. Article
  3. The lactate sensor NDRG3 decelerates ER-to-Golgi transport through interaction with the long isoform of syntaxin-5.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Article
  5. Article
  6. Article
  7. Exocytic machineries differentially control mediator release from allergen-triggered RBL-2H3 cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Article
  8. Review
  9. Article
  10. The function of VAMP2 in mediating membrane fusion: An overview.Frontiers in molecular neuroscience · 2022
    Review
  11. Article
  12. Article
  13. Review
  14. Chaperoning SNARE Folding and Assembly.Annual review of biochemistry · 2021
    Review
  15. Article
  16. A conformational switch driven by phosphorylation regulates the activity of the evolutionarily conserved SNARE Ykt6.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  17. Article
  18. Review
  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

12 authors at 3 institutions in 2 countries.

Seth MalmersjöDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA, USA sethma@stanford.edu tobias1@stanford.edu.ORCID 0000-0002-1519-8916
Serena Di PalmaInstitute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland Functional Genomics Center Zurich, ETH Zurich/University of Zurich, Zurich, Switzerland.
Jiajie DiaoDepartments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Photon Science, and Structural Biology, Stanford University, Stanford, CA, USA Howard Hughes Medical Institute, Stanford, CA, USA.ORCID 0000-0003-4288-3203
Ying LaiDepartments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Photon Science, and Structural Biology, Stanford University, Stanford, CA, USA Howard Hughes Medical Institute, Stanford, CA, USA.
Richard A PfuetznerDepartments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Photon Science, and Structural Biology, Stanford University, Stanford, CA, USA Howard Hughes Medical Institute, Stanford, CA, USA.
Austin L WangDepartments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Photon Science, and Structural Biology, Stanford University, Stanford, CA, USA Howard Hughes Medical Institute, Stanford, CA, USA.
Moira A McMahonDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Arnold HayerDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.
Matthew PorteusDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Bernd BodenmillerInstitute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Axel T BrungerDepartments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Photon Science, and Structural Biology, Stanford University, Stanford, CA, USA Howard Hughes Medical Institute, Stanford, CA, USA.
Tobias MeyerDepartment of Chemical and Systems Biology, Stanford University, Stanford, CA, USA sethma@stanford.edu tobias1@stanford.edu.ORCID 0000-0003-4339-3804
Howard Hughes Medical Institute · USStanford University · USUniversity of Zurich · CH

Funding

TRAINING & OUTREACH COREP50GM107615 · NIGMS · STANFORD UNIVERSITY · PI FERRELL, JAMES E. · 2013 to 2017
$10.9M
REGULATION OF CA++/CALMODULIN KINASE BY NEUROTRANSMITTERR01GM030179 · NIGMS · STANFORD UNIVERSITY · PI MEYER, TOBIAS · 1985 to 2018
$4.9M
Single molecule studies of SNARE-induced vesicle fusionR37MH063105 · NIMH · STANFORD UNIVERSITY · PI BRUNGER, AXEL T · 2011 to 2020
$4.7M
REGULATION OF CA++/CALMODULIN KINASE BY NEUROTRANSMITTERR37GM030179 · NIGMS · STANFORD UNIVERSITY · PI MEYER, TOBIAS · 1995 to 2004
$1.7M
CV7000S10OD018073 · OD · STANFORD UNIVERSITY · PI MEYER, TOBIAS · 2014 to 2014
$599k
European Research Council 336921NIGMS NIH HHS P50 GM107615NIGMS NIH HHS R01 GM030179NIGMS NIH HHS R37 GM030179NIH HHS S10 OD018073NIMH NIH HHS R37 MH063105
6 · The paper itself

Abstract

Membrane fusion is essential for eukaryotic life, requiring SNARE proteins to zipper up in an α-helical bundle to pull two membranes together. Here, we show that vesicle fusion can be suppressed by phosphorylation of core conserved residues inside the SNARE domain. We took a proteomics approach using a PKCB knockout mast cell model and found that the key mast cell secretory protein VAMP8 becomes phosphorylated by PKC at multiple residues in the SNARE domain. Our data suggest that VAMP8 phosphorylation reduces vesicle fusion in vitro and suppresses secretion in living cells, allowing vesicles to dock but preventing fusion with the plasma membrane. Markedly, we show that the phosphorylation motif is absent in all eukaryotic neuronal VAMPs, but present in all other VAMPs. Thus, phosphorylation of SNARE domains is a general mechanism to restrict how much cells secrete, opening the door for new therapeutic strategies for suppression of secretion.

Indexed as

Protein Processing, Post-TranslationalAnimalsCell LineMast CellsPhosphorylationProtein Kinase CProteomicsRatsR-SNARE ProteinsSecretory VesiclesProtein Kinase CR-SNARE ProteinsVamp8 protein, ratmast cell degranulationprotein kinase CsecretionSNARE complexVAMP8

Identifiers

PMID27402227
PMCPMC5010044
OpenAlexW2461334745

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.