Publication Date:
2006-03-18
Description:
How the widely used botulinum neurotoxin A (BoNT/A) recognizes and enters neurons is poorly understood. We found that BoNT/A enters neurons by binding to the synaptic vesicle protein SV2 (isoforms A, B, and C). Fragments of SV2 that harbor the toxin interaction domain inhibited BoNT/A from binding to neurons. BoNT/A binding to SV2A and SV2B knockout hippocampal neurons was abolished and was restored by expressing SV2A, SV2B, or SV2C. Reduction of SV2 expression in PC12 and Neuro-2a cells also inhibited entry of BoNT/A, which could be restored by expressing SV2 isoforms. Finally, mice that lacked an SV2 isoform (SV2B) displayed reduced sensitivity to BoNT/A. Thus, SV2 acts as the protein receptor for BoNT/A.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dong, Min -- Yeh, Felix -- Tepp, William H -- Dean, Camin -- Johnson, Eric A -- Janz, Roger -- Chapman, Edwin R -- R01 EY016452/EY/NEI NIH HHS/ -- R01 EY016452-03/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2006 Apr 28;312(5773):592-6. Epub 2006 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Physiology, University of Wisconsin, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16543415" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Botulinum Toxins, Type A/*metabolism/toxicity
;
Cell Line
;
Cells, Cultured
;
Endocytosis
;
Hippocampus/cytology
;
Membrane Glycoproteins/chemistry/genetics/*metabolism
;
Mice
;
Mice, Knockout
;
Nerve Tissue Proteins/chemistry/genetics/*metabolism
;
Neuromuscular Junction/metabolism
;
Neurons/*metabolism
;
PC12 Cells
;
Protein Binding
;
Protein Isoforms/chemistry/genetics/metabolism
;
Protein Structure, Tertiary
;
R-SNARE Proteins/metabolism
;
Rats
;
Synaptic Vesicles/*metabolism
;
Synaptotagmins/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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