Title: Lipid rafts: inhibitors of endocytosis of botulinum neurotoxin

Authors: Kimberly A. Petro, Cara-Lynne Schengrund

Addresses: Bio-Rad Life Science Group, 5353 La Jolla Blvd. #33, La Jolla, CA 92037, USA. ' Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA

Abstract: Methyl-ß-cyclodextrin (MßCD) was used to extract cholesterol from plasma membranes of N2a murine neuroblastoma cells. MßCD-disruption of lipid rafts enhanced cleavage of SNAP-25 by BoNT/A, axonogenesis, expression of gangliosides GM1 and GD1a, association of GM1 with the nucleus, and exo- and endo-cytosis. Analysis of endocytosis of an anti-synaptotagmin I monoclonal antibody that recognised part of the protein found on the luminal surface of synaptic vesicles indicated that it was taken up more readily by MßCD-treated cells, supporting the hypothesis that enhanced exocytosis of synaptic vesicles provided more SV2 on the cell surface thereby making more available for toxin binding.

Keywords: BoNT/A; botulinum neurotoxin serotype A; lipid rafts; methyl-beta-cyclodextrin; synaptotagmin I; endocytosis; gangliosides vesicles; synaptic vesicles; monoclonal antibodies; toxin binding; BoNT; botulism.

DOI: 10.1504/TBJ.2010.039112

The Botulinum Journal, 2010 Vol.1 No.4, pp.358 - 374

Published online: 17 Mar 2011 *

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