Special Issue "Neurotoxins of Biological Origin"

Guest Editor
Prof. Dr. Anthony T. Tu
Department of Biochemistry and Molecular Biology, Colorado State University, Ft. Collins, CO 80523, USA
E-Mail:
Interests: snake venoms; sea snake neurotoxins; Raman spectroscopy; structure-function relations of toxins; chemical weapons defense; NBCR anti-terrorism

Dear Colleagues,

The word “neurotoxins” attracts the interest if scientists and laymen alike. Neutoroxins can be of many different types with diverse origins, including both synthetic and naturally derived toxins. DDT, organophosphate insecticides, and nerve gases such as sarin, tabun, and VX are all neurotoxic, but the mechanisms of action can be different. Likewise, biological neurotoxins are also very complex and each toxin differs in binding site, source, and mechanism of toxic action. They may act on the axon, presynaptic site, or the postsynaptic site of the acetylcholine receptor. Some toxins even affect the axon’s sodium channel with different binding sites. Tetradotoxin (Fugu toxin) blocks the entrance of the sodium gate, while scorpion toxin binds to the interior portion of the sodium channel. Tetanus toxin enters the peripheral nervous system from the neuromuscular junction, travels through the inside of the axon, and stops at the place where the peripheral and central nerves connect. Because each toxin differs in action and binding site, this specificity can be used to study individual sites of the nervous system. For this reason, neurotoxins are considered good tools for the understanding of this complex system. In this special review, I asked experts of biological neurotoxins to contribute chapters to increase the understanding of different aspects of neurotoxins.

Anthony T. Tu
Guest Editor

Submission

All manuscripts should be submitted to toxins@mdpi.org with a copy to the Guest Editor. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed Open Access monthly journal published by MDPI.

• Natural poisons
• Neurotoxins of natural origin
• Neurotoxins of biological origin
• Botulinum toxin
• Phospholipase A2 snake neurotoxin
• Spider neurotoxin

Type of Paper: Review
Title: Clostridial Neurotoxins and Other Bacterial Toxins Affecting the Nervous System
Author: Michel R. Popoff; E-Mail: mpopoff@pasteur.fr
Affiliation: CNR Anaerobies et Botulisme, Unite Bacteries anaerobies et Toxines, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris, cedex 15, France; Ph: +33 1 45 68 83 07
Abstract: Clostridial neurotoxins, botulinum neurotoxins (BoNTs) and tetanus toxin (TeNT), are the most potent toxins known. BoNTs specifically target neuromuscular junctions and TeNT triggers a retrograde axonal transport and reaches inhibitory interneurons in the central nervous system. Both toxin types inhibit the release of neurotransmitter by proteolytic cleavage of SNARE proteins, which are specific of the neuroexocytosis machinery. Other bacterial toxins target neuronal cells in addition to other cell types and impair neuronal activity such as Clostridium perfringens epsilon toxin, which enhances the glutamate release, and clostridial glucosylating toxins which inactivate Rho-GTPases, molecules having a role in the neuroexocytosis. Bacterial enterotoxins such as Staphylococcus enterotoxins directly interact with the enteric nervous system.

Type of Paper: Article
Title: Functional Analysis of Synaptotagmin II as a Receptor for Clostridium botulinum type B Neurotoxin
Authors: Tomoko Kohda ¹, Hideshi Ihara ², Masafumi Mukamoto ¹ and Shunji Kozaki ¹
Affiliations: ¹ Department of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan; E-Mails: kohda@vet.osakafu-u.ac.jp (T.K.); kozaki@center.osakafu-u.ac.jp (S.K.)
² Department of Biological Science, Graduate School of Sciences, Osaka Prefecture University, Osaka, Japan
Abstract: Botulinum neurotoxin (BoNT) binds to presynaptic nerve terminals by recognizing specific neuronal surface receptors and blocks neurotransmitter release. We demonstrated that two homologous synaptic vesicle membrane proteins, synaptotagmin (Stg) I and II associated with ganglioside GT1b is the receptor for BoNT/B. The luminal domain of StgII associated with ganglioside GT1b forms the high-affinity toxin binding site. In this study, we generated StgII expressed PC12 cells transiently and applied to understand more precisely how BoNT/B recognizes the receptor and enters neurons. Rat full-length StgII gene was subcloned into pcDNA 3.2/V5-DEST vector and transfected into PC12 cells using lipid transfection. The functional entry of BoNT/B was determined by monitoring K+-evoked dopamine release and VAMP2 amount in the cells. We found that BoNT/B caused the inhibition of dopamine release and VAMP2 proteolysis in the transfected PC12 cells. The findings confirmed that StgII can function as a receptor for BoNT/B. We then examined the toxin sensitivity of StgII-expressing cells after treatment with exogenous gangliosides. BoNT/B showed more effective to the treated cells. The result supports the notion that StgII and ganglioside cooperate to play a role in BoNT/B receptor. In addition we have generated transformant of PC12 cells expressed mutagenesis by exchanging residues within StgII affect binding of BoNT/B. The results on toxin action of their mutants may exhibit exactly the binding site and reveal receptor recognition by BoNT/B.