Evidence map›Paper›PMID 22454523›Full record

ArticleJournal of cell science2012

Botulinum neurotoxin D-C uses synaptotagmin I and II as receptors, and human synaptotagmin II is not an effective receptor for type B, D-C and G toxins.

Lisheng Peng, Ronnie P-A Berntsson, William H Tepp, Rose M Pitkin, Eric A Johnson, Pål Stenmark, Min Dong

Open access · bronzeAbstract read
In one paragraph

Article in Journal of cell science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 1 pooled it
6.2field-weighted citation impact, top 3% 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, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.

  1. Guideline
  2. Article
  3. Therapeutic botulinum toxin preparations: an update.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. The Structure and Classification of Botulinum Toxins.Handbook of experimental pharmacology · 2021
    Article
  18. The 25 kDa HToxins · 2020
    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

7 authors at 3 institutions in 2 countries.

Lisheng PengDepartment of Microbiology and Immunobiology, Harvard Medical School and Division of Neuroscience, New England Primate Research Center, Southborough, MA 01772, USA.
Ronnie P-A Berntsson
William H Tepp
Rose M Pitkin
Eric A Johnson
Pål Stenmark
Min Dong
Harvard University · USStockholm University · SEUniversity of Wisconsin–Madison · 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
Treatments for Nipah Virus InfectionU54AI057159 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI KASPER, DENNIS L. · 2003 to 2013
$113.7M
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
MOUSE MODELS OF CANCER, BONE DISEASE, AND LACTATIONK26RR000168 · NCRR · OHIO STATE UNIVERSITY · PI ROSOL, THOMAS J · 2000 to 2004
$547k
NCRR NIH HHS K26 RR000168NCRR NIH HHS P51 RR000168NCRR NIH HHS RR000168NIAID NIH HHS U54 AI057159NIH HHS 8P51OD011103-51NIH HHS P51 OD011103NINDS NIH HHS R01 NS080833
6 · The paper itself

Abstract

Botulinum neurotoxins (BoNTs) are classified into seven types (A-G), but multiple subtype and mosaic toxins exist. These subtype and mosaic toxins share a high sequence identity, and presumably the same receptors and substrates with their parental toxins. Here, we report that a mosaic toxin, type D-C (BoNT/D-C), uses different receptors from its parental toxin BoNT/C. BoNT/D-C, but not BoNT/C, binds directly to the luminal domains of synaptic vesicle proteins synaptotagmin (Syt) I and II, and requires expression of SytI/II to enter neurons. The SytII luminal fragment containing the toxin-binding site can block the entry of BoNT/D-C into neurons and reduce its toxicity in vivo in mice. We also found that gangliosides increase binding of BoNT/D-C to SytI/II and enhance the ability of the SytII luminal fragment to block BoNT/D-C entry into neurons. These data establish SytI/II, in conjunction with gangliosides, as the receptors for BoNT/D-C, and indicate that BoNT/D-C is functionally distinct from BoNT/C. We further found that BoNT/D-C recognizes the same binding site on SytI/II where BoNT/B and G also bind, but utilizes a receptor-binding interface that is distinct from BoNT/B and G. Finally, we also report that human and chimpanzee SytII has diminished binding and function as the receptor for BoNT/B, D-C and G owing to a single residue change from rodent SytII within the toxin binding site, potentially reducing the potency of these BoNTs in humans and chimpanzees.

Indexed as

Amino Acid SequenceAnimalsBinding SitesBotulinum ToxinsBotulinum Toxins, Type ACells, CulturedClostridium botulinumExocytosisHippocampusHumansLethal Dose 50MiceMolecular Sequence DataNeuronsProtein BindingProtein Structure, TertiaryBotulinum ToxinsBotulinum Toxins, Type Abotulinum toxin type Cbotulinum toxin type Dbotulinum toxin type GReceptors, Cell SurfacerimabotulinumtoxinBSynaptotagmin ISynaptotagmin IISyt1 protein, ratSYT2 protein, human

Identifiers

PMID22454523
PMCPMC4067266
OpenAlexW2128833323

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.