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. |