Tetanus toxin (TeNT), a disulfide-bonded heavy chain (HC) - light chain (LC) dimer, is secreted from bacteria growing in an infected wound directly into the circulation. Circulating toxin molecules associate with gangliosides at a synapse of a target neuron. The toxin is taken up into clathrin-coated vesicles that reach the neuron cell body by retrograde transport and then possibly other neurons before undergoing acidification. Vesicle acidification causes a conformational change in the toxin, allowing its HC part to function as a channel through which its LC part is extruded into the neuronal cytosol. Cleavage of the HC - LC disulfide bond releases the LC into the cytosol, where it functions as a zinc metalloprotease to cleave vesicle-associated membrane protein 2 (VAMP2), thereby blocking synaptic vesicle exocytosis (Lalli et al. 2003)

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