Tetanus Activation mechanism

Several groups have studied the effects on the muscle low-angle diffraction pattern of applying various mechanical perturbations to steady-state structures, either isometric contractions or rigor muscle at various strain levels. Huxley et al. (1981, 1983) used whole frog muscles and followed the effects of step changes of length of various amplitudes applied at the plateau of an otherwise isometric tetanus. They studied the effects on the M3 intensity as a whole. More recendy, with the two components of the active M3 resolved, Huxley et al. (2003) and Reconditi et al. (2003) have studied the separate behavior of these components. Huxley et al. (2003) found that the intensity ratio of the M30 to M3 varied from an initial value... 

Fig. 1. The mechanism of activation of tetanus and botulinum neurotoxins. The toxins are produced as an inactive single polypeptide chain of 150 kDa, composed of three 50 kDa domains, connected by protease-sensitive loops. The toxins are activated by selective proteolytic cleavage which generates two disulfide-linked chains L (50kDa) and H (100kDa). The three domains play different functional roles in cell penetration He is responsible for cell binding and Hn for cell penetration. Reduction takes place inside the nerve cells and liberates the metallo-protease activity of fhe L chain in the cytosol...

Eddinger TJ, Murphy RA (1991) Developmental changes in actin and myosin heavy chain isoform expression in smooth muscle. Arch Biochem Biophys 284 232237 Eddinger TJ, Wolf JA (1993) Expression of four myosin heavy chain isoforms with development iii mouse uterus. Cell Motil Cytoskeleton 25 358368 Edman KA (1980) Depression of mechanical performance by active shortening during twitch and tetanus of vertebrate muscle fibres. Acta Physiologica Scandinavica 109 1526... 

An alternative mechanism of the involvement of the transglutaminase catalyzed immobilization of the synaptic vesicles have been proposed for tetanus-induced blockage of the neurotransmitter release (Facchiano et al., 1993). In the past, attempts have been made to demonstrate ADP-ribosyl transferase activity in botulinum neurotoxins (cf. Singh, 1990) without any success. The hypothesis of ADP-ribosyl transferase activity of botulinum neurotoxins derives from analogies with diphtheria, cholera and botulinum C2 toxins, all with similar extracellular mode of action (Simpson, 1989b). 

---