Title: The inveterate botulinum neurotoxin A ushers in exo-endocytic crypts

Authors: Joseph G. Potian, Vishwendra Patel, Joseph J. McArdle, Baskaran Thyagarajan

Addresses: Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA. ' Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA. ' Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA. ' Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA

Abstract: Botulinum neurotoxins (BoNTs), serotypes A through G (BoNT/A to BoNT/G) are potential bioweapons and are extensively used clinically. Although the mechanism of BoNT/A cleavage of SNAP25 is well characterised, little is known regarding the uptake of BoNT/A at the Motor Nerve Terminal (MNT). We demonstrate that BoNT/A uses Clathrin Coated Pit (CCP) dependent mechanisms for endocytosis and that disruption of CCP reduces BoNT/A uptake into mouse MNTs and Neuro 2a cells. This presents a novel strategy for protection against BoNT/A. Our data stimulate the exploration of BoNT/A – interactome signalling for the development of prophylactics as well as therapeutics against botulism.

Keywords: botulinum neurotoxin; clathin coated pits; endocytosis; exocytosis; motor nerve terminals; BoNT/A; BoNT; botulism; prophylactics; therapeutics; interactome signalling; nerve ends.

DOI: 10.1504/TBJ.2010.039116

The Botulinum Journal, 2010 Vol.1 No.4, pp.418 - 430

Published online: 17 Mar 2011 *

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