Evidence map›Paper›PMID 18815274›Full record

ArticleMolecular biology of the cell2008

Glycosylated SV2A and SV2B mediate the entry of botulinum neurotoxin E into neurons.

Min Dong, Huisheng Liu, William H Tepp, Eric A Johnson, Roger Janz, Edwin R Chapman

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed, 1 pooled it
10.5field-weighted citation impact, top 1% 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

121 citing papers in PubMed, 1 synthesis or guideline pooled it, 232 citations in OpenAlex.

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  19. Advances in Clostridial and Related Neurotoxins.International journal of molecular sciences · 2022
    Article
  20. Article

61 more citing papers are in PubMed but not listed here.

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

6 authors at 3 institutions in 1 country.

Min DongHoward Hughes Medical Institute and Department of Physiology, University of Wisconsin, Madison, WI 53706, USA.
Huisheng Liu
William H Tepp
Eric A Johnson
Roger Janz
Edwin R Chapman
Howard Hughes Medical Institute · USUniversity of Wisconsin–Madison · USThe University of Texas Health Science Center at Houston · US

Funding

Vaccines and Therapies Against BotulismU54AI057153 · NIAID · UNIVERSITY OF CHICAGO · PI SCHNEEWIND, OLAF · 2003 to 2013
$87.6M
Structural Basis of Immune Recognition of Glycosylated AntigensU54GM062116 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI SASISEKHARAN, RAM · 2001 to 2010
$80.3M
Receptors for clostridial neurotoxinsR01AI057744 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI CHAPMAN, EDWIN R · 2004 to 2008
$1.7M
Role of SV2B in Ribbon Synapses of the RetinaR01EY016452 · NEI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI JANZ, ROGER · 2005 to 2008
$1.4M
Howard Hughes Medical InstituteNEI NIH HHS EY016452NEI NIH HHS R01 EY016452NIAID NIH HHS 1-U54-AI-057153NIAID NIH HHS R01 AI057744NIAID NIH HHS U54 AI057153NIGMS NIH HHS GM62116NIGMS NIH HHS U54 GM062116
6 · The paper itself

Abstract

Botulinum neurotoxin E (BoNT/E) can cause paralysis in humans and animals by blocking neurotransmitter release from presynaptic nerve terminals. How this toxin targets and enters neurons is not known. Here we identified two isoforms of the synaptic vesicle protein SV2, SV2A and SV2B, as the protein receptors for BoNT/E. BoNT/E failed to enter neurons cultured from SV2A/B knockout mice; entry was restored by expressing SV2A or SV2B, but not SV2C. Mice lacking SV2B displayed reduced sensitivity to BoNT/E. The fourth luminal domain of SV2A or SV2B alone, expressed in chimeric receptors by replacing the extracellular domain of the low-density lipoprotein receptor, can restore the binding and entry of BoNT/E into neurons lacking SV2A/B. Furthermore, we found disruption of a N-glycosylation site (N573Q) within the fourth luminal domain of SV2A rendered the mutant unable to mediate the entry of BoNT/E and also reduced the entry of BoNT/A. Finally, we demonstrate that BoNT/E failed to bind and enter ganglioside-deficient neurons; entry was rescued by loading exogenous gangliosides into neuronal membranes. Together, the data reported here demonstrate that glycosylated SV2A and SV2B act in conjunction with gangliosides to mediate the entry of BoNT/E into neurons.

Indexed as

Virus InternalizationAmino Acid SequenceAnimalsBotulinum ToxinsCells, CulturedGangliosidesGlycosylationHippocampusHumansMembrane GlycoproteinsMembrane PotentialsMiceMice, KnockoutMolecular Sequence DataNerve Tissue ProteinsNeuronsBotulinum Toxinsbotulinum toxin type EGangliosidesMembrane GlycoproteinsNerve Tissue ProteinsProtein IsoformsRecombinant Fusion ProteinsSv2a protein, mouseSv2b protein, mouse

Identifiers

PMID18815274
PMCPMC2592654
OpenAlexW2132639205

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.