Botulinum toxins genetics

Norgauer, J., Kownatzki, E Seifert, R., and Aktories, K. (1988) Botulinum C2 toxin ADP-ribosylates actin and enhances 02 production and secretion but inhibits migration of activated human neutrophils. J. Clin. Invest. 82,1376-1382. Boxer, L. A., Hedley-Whyte, E. T and Stossel, T. P. (1974) Neutrophil actin dysfunction and abnormal neutrophil behavior. N. Engl. J. Med. 291,1093-1099. Southwick, E. S., Dabiri, G. A., and Stossel, T. P. (1988) Neutrophil actin dysfunction is a genetic disorder associated with partial impairment of neutrophil actin assembly in three family members. J. Clin. Invest. 82, 1525-1531. 

Medical personnel must remember, however, that with the advances of molecular genetics, it is possible to clone and produce many natural neurotoxins in relatively large quantities. For the present (1996), botulinum poisoning is a much more likely biological warfare agent than snake venom toxins. In future years, other (cloned) neurotoxins should be considered in the diagnosis. 

Amperometry at single PC 12 cells has also been used in conjunction with a genetic cell transfection protocol to examine the effects of toxin expression on basal and evoked exocytosis. PC 12 cells have been transfected with the specific endoprotease Botulinum neurotoxin Cl light chain (BoNT/Cl), which cleaves the proteins syntaxin and SNAP-25 [5], The molecular dissection of the mechanisms underlying exocytosis has been motivated by the SNARE hypothesis, which postulates that exocytosis requires the assembly of the plasma membrane proteins syntaxin 1, SNAP-25, and the vesicle associated membrane protein (VAMP) into a complex [5], This SNARE complex then acts as a receptor for cytosolic components of the proposed fusion machinery. Direct evidence for the role of the SNARE proteins in neurotransmission comes from molecular genetic studies in which syntaxin and VAMP have been shown to be required for neurotransmission in Drosophila [47 9] and Caenorhabditis elegans [50,51]. To assess the effects of the disruption of SNARE proteins on exocytosis in PC 12 cells, amperometry has been used in conjunction with a genetic cell transfection assay to establish a... 

---