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Publication : Mechanism of botulinum neurotoxin B and G entry into hippocampal neurons.

First Author  Dong M Year  2007
Journal  J Cell Biol Volume  179
Issue  7 Pages  1511-22
PubMed ID  18158333 Mgi Jnum  J:135458
Mgi Id  MGI:3793895 Doi  10.1083/jcb.200707184
Citation  Dong M, et al. (2007) Mechanism of botulinum neurotoxin B and G entry into hippocampal neurons. J Cell Biol 179(7):1511-22
abstractText  Botulinum neurotoxins (BoNTs) target presynaptic nerve terminals by recognizing specific neuronal surface receptors. Two homologous synaptic vesicle membrane proteins, synaptotagmins (Syts) I and II, bind toxins BoNT/B and G. However, a direct demonstration that Syts I/II mediate toxin binding and entry into neurons is lacking. We report that BoNT/B and G fail to bind and enter hippocampal neurons cultured from Syt I knockout mice. Wild-type Syts I and II (but not Syt I loss-of-function toxin-binding domain mutants) restored binding and entry of BoNT/B and G in Syt I-null neurons, thus demonstrating that Syts I/II are protein receptors for BoNT/B and G. Furthermore, mice lacking complex gangliosides exhibit reduced sensitivity to BoNT/G, and binding and entry of BoNT/A, B, and G into hippocampal neurons lacking gangliosides is diminished. These data suggest that gangliosides are the shared coreceptor for BoNT/A, B, and G, supporting a double-receptor model for these three BoNTs for which the protein receptors are known.
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