Lipid rafts: inhibitors of endocytosis of botulinum neurotoxin

Authors: Petro, Kimberly A.¹; Schengrund, Cara-Lynne²

Source: The Botulinum J., Volume 1, Number 4, March 2010 , pp. 358-374(17)

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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: HEALTHCARE AND BIOSCIENCES; Biosciences and Bioinformatics; Healthcare and Medical Engineering

Document Type: Research article

DOI: http://dx.doi.org/10.1504/TBJ.2010.039112

Affiliations: 1: Bio-Rad Life Science Group, 5353 La Jolla Blvd. #33, La Jolla, CA 92037, USA. 2: Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA

Publication date: 2010-03-01

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The objectives of The Botulinum Journal are to disseminate knowledge, provide a learned reference in the field, and establish channels of communication amongst academic, medical, and public health research experts, pharmaceutical industry, cosmetic industry, policy makers and executives in industry, commerce and investment institutions. The Botulinum Journal will provide a forum to exchange scholarly ideas relevant to health, science, application, and regulatory issues related to the botulinum neurotoxin and Clostridium botulinum.