Evidence map›Paper›PMID 25010769›Full record

ArticlePLoS pathogens2014

Widespread sequence variations in VAMP1 across vertebrates suggest a potential selective pressure from botulinum neurotoxins.

Lisheng Peng, Michael Adler, Ann Demogines, Andrew Borrell, Huisheng Liu, Liang Tao, William H Tepp, Su-Chun Zhang, Eric A Johnson, Sara L Sawyer and 1 more

Open access · goldAbstract readComparative Study
In one paragraph

Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

22 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Botulinum and Tetanus Neurotoxins.Annual review of biochemistry · 2019
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  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

11 authors at 4 institutions in 1 country.

Lisheng PengDepartment of Microbiology and Immunobiology, Harvard Medical School and Division of Neuroscience, New England Primate Research Center, Southborough, Massachusetts, United States of America.
Michael AdlerNeurobehavioral Toxicology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Aberdeen, Maryland, United States of America.
Ann DemoginesDepartment of Molecular Biosciences, University of Texas, Austin, Texas, United States of America.
Andrew BorrellNeurobehavioral Toxicology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Aberdeen, Maryland, United States of America.
Huisheng LiuWaisman Center, Department of Neuroscience, Department of Neurology, University of Wisconsin, Madison, Wisconsin, United States of America.
Liang TaoDepartment of Microbiology and Immunobiology, Harvard Medical School and Division of Neuroscience, New England Primate Research Center, Southborough, Massachusetts, United States of America.
William H TeppDepartment of Bacteriology, University of Wisconsin, Madison, Wisconsin, United States of America.
Su-Chun ZhangWaisman Center, Department of Neuroscience, Department of Neurology, University of Wisconsin, Madison, Wisconsin, United States of America.
Eric A JohnsonDepartment of Bacteriology, University of Wisconsin, Madison, Wisconsin, United States of America.
Sara L SawyerDepartment of Molecular Biosciences, University of Texas, Austin, Texas, United States of America.
Min DongDepartment of Microbiology and Immunobiology, Harvard Medical School and Division of Neuroscience, New England Primate Research Center, Southborough, Massachusetts, United States of America.
University of Wisconsin–Madison · USHarvard University · USThe University of Texas at Austin · USUnited States Army · US

Funding

ZETA CHAIN OF T CELL RECEPTOR INTERACTS W/ NEF OF SIV &HIV2P51RR000168 · NCRR · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WESTMORELAND, SUSAN V. · 1985 to 2011
$139.3M
WISCONSIN CENTER ON MENTAL RETARDATION: CORE SUPPORTP30HD003352 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI SVAREN, JOHN P · 1985 to 2015
$25.2M
New England Primate Research Center Base GrantP51OD011103 · OD · HARVARD MEDICAL SCHOOL · PI FLIER, JEFFREY S · 2012 to 2013
$24.7M
Long-term effects of botulinum neurotoxins on neuronal viabilityR01NS080833 · NINDS · HARVARD MEDICAL SCHOOL · PI Min Dong · 2013 to 2026
$6.8M
Rapid evolution of genes critical for genome integrityR01GM093086 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI SAWYER, SARA · 2010 to 2016
$1.9M
MOUSE MODELS OF CANCER, BONE DISEASE, AND LACTATIONK26RR000168 · NCRR · OHIO STATE UNIVERSITY · PI ROSOL, THOMAS J · 2000 to 2004
$547k
Next generation of botulinum neurotoxins with enhanced binding to human receptorsR21NS082830 · NINDS · HARVARD MEDICAL SCHOOL · PI DONG, MIN · 2013 to 2014
$479k
Cytotoxicity of botulinum neurotoxinsR56AI097834 · NIAID · HARVARD MEDICAL SCHOOL · PI DONG, MIN · 2012 to 2012
$438k
NCRR NIH HHS K26 RR000168NCRR NIH HHS P51 RR000168NCRR NIH HHS RR000168NIAID NIH HHS 1R56AI097834NIAID NIH HHS R56 AI097834NICHD NIH HHS P30 HD003352NIGMS NIH HHS R01 GM093086NIGMS NIH HHS R01-GM-093086NIH HHS OD011103NIH HHS P51 OD011103NINDS NIH HHS 1R01NS080833NINDS NIH HHS 1R21NS082830NINDS NIH HHS R01 NS080833NINDS NIH HHS R21 NS082830
6 · The paper itself

Abstract

Botulinum neurotoxins (BoNT/A-G), the most potent toxins known, act by cleaving three SNARE proteins required for synaptic vesicle exocytosis. Previous studies on BoNTs have generally utilized the major SNARE homologues expressed in brain (VAMP2, syntaxin 1, and SNAP-25). However, BoNTs target peripheral motor neurons and cause death by paralyzing respiratory muscles such as the diaphragm. Here we report that VAMP1, but not VAMP2, is the SNARE homologue predominantly expressed in adult rodent diaphragm motor nerve terminals and in differentiated human motor neurons. In contrast to the highly conserved VAMP2, BoNT-resistant variations in VAMP1 are widespread across vertebrates. In particular, we identified a polymorphism at position 48 of VAMP1 in rats, which renders VAMP1 either resistant (I48) or sensitive (M48) to BoNT/D. Taking advantage of this finding, we showed that rat diaphragms with I48 in VAMP1 are insensitive to BoNT/D compared to rat diaphragms with M48 in VAMP1. This unique intra-species comparison establishes VAMP1 as a physiological toxin target in diaphragm motor nerve terminals, and demonstrates that the resistance of VAMP1 to BoNTs can underlie the insensitivity of a species to members of BoNTs. Consistently, human VAMP1 contains I48, which may explain why humans are insensitive to BoNT/D. Finally, we report that residue 48 of VAMP1 varies frequently between M and I across seventeen closely related primate species, suggesting a potential selective pressure from members of BoNTs for resistance in vertebrates.

Indexed as

Genetic VariationVesicle-Associated Membrane Protein 1Amino Acid SequenceAnimalsBotulinum ToxinsDiaphragmHumansMaleMiceMolecular Sequence DataMotor NeuronsParesisRatsRats, Sprague-DawleySpecies SpecificityBotulinum ToxinsVAMP1 protein, humanVesicle-Associated Membrane Protein 1vesicle-associated membrane protein 1, mousevesicle-associated membrane protein 1, rat

Identifiers

PMID25010769
PMCPMC4092145
OpenAlexW2111960578

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.