Gangliosides Interact with Synaptotagmin to Form the High-Affinity Receptor Complex for Botulinum Neurotoxin B
Gangliosides interact with synaptotagmin to form the high-affinity receptor complex for botulinum neurotoxin B Alessandra Floresa,b,1, Jorge Ramirez-Francoa,b,1, Richard Desplantesa,b, Kévin Debreuxa,b, Géraldine Ferraccib,c, Florian Wernerta,b, Marie-Pierre Blanchardb,c, Yves Mauleta,b, Fahamoe Youssoufa,b, Marion Sangiardia,b, Cécile Iborraa,b, Michel Robert Popoffd, Michael Seagara,b, Jacques Fantinia,b, Christian Lévêquea,b, and Oussama El Fara,b,2 aUnité de Neurobiologie des Canaux Ioniques et de la Synapse, INSERM UMR_S 1072, 13015 Marseille, France; bAix-Marseille Université, 13015 Marseille, France; cInstitut de Neurophysiopathologie, CNRS UMR 7051, 13015 Marseille, France; and dBacterial Toxins, Équipe de Recherche Labellisée 6002, Institut Pasteur, 75015 Paris, France Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved August 1, 2019 (received for review May 15, 2019) Botulinum neurotoxin type B (BoNT/B) recognizes nerve terminals synaptic vesicle proteins that become accessible at the presynaptic by binding to 2 receptor components: a polysialoganglioside, membrane upon exocytosis. BoNT/A and E bind to the synaptic predominantly GT1b, and synaptotagmin 1/2. It is widely thought vesicle protein 2 (SV2), while BoNT/B binds synaptotagmin (SYT that BoNT/B initially binds to GT1b then diffuses in the plane of isoforms 1 and 2). the membrane to interact with synaptotagmin. We have addressed Gangliosides are amphiphilic glycosphingolipid molecules the hypothesis that a GT1b–synaptotagmin cis complex forms the predominantly anchored, via their ceramide group, in the outer BoNT/B receptor. We identified a consensus glycosphingolipid-binding leaflet of plasma membranes. Their extracellular polar part is motif in the extracellular juxtamembrane domain of synaptotagmins composed of several characteristic sugar molecules with the 1/2 and confirmed by Langmuir monolayer, surface plasmon reso- negatively charged sialic acids at precise positions.
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