Endocytosis Diphtheria toxin

Keen, J.H., Maxfield, F.R., Hardegree, M.C., and Habig, W.H. (1982) Receptor-mediated endocytosis of diphtheria toxin by cell in culture. Proc. Natl Acad. Sci. USA 79, 2912. 

Receptor-mediated endocytosis is exploited by some toxins and viruses to gain entry to cells. Influenza virus (see Fig. 11-24), diphtheria toxin, and cholera toxin all enter cells in this way. 

Lanzrein M, Garred 0, Olsnes S, Sandvig K (1995) Diphtheria toxin endocytosis and membrane translocation is dependent on the intact membrane anchored receptor (HB-EGF precursor) Studies on the cell-associated receptor cleaved by a metalloprotease in TPA-treated cells. Biochem J 310 285-289. 

They bind initially to ganglioside in the neuromuscular jimction, one subunit then being internalized as with the diphtheria toxin (Box 29-A). Botulinum toxins specifically enter motor neurons, while tetanus toxin is taken up via synaptic vesicle endocytosis by both peripheral and central neurons. Retrograde axonal transport carries the toxin into the central nervous system and across synaptic clefts into cholinergic intemeurons, which are poisoned. 

In conformity with the sequential processing of bacterial protein toxins such as diphtheria or cholera toxin, the action of BoNT involves multiple discrete steps binding to surface receptors, internalization via receptor-mediated endocytosis, transport from endosome to cytosol, and cleavage of target proteins in the cytosol. " Binding and internalization are mediated by the C- and N-terminal domains of the BoNT H-chain, respectively. The L-chains have zinc metalloprotease activity, targeted selectively to one of three proteins that are required for the docking and fusion of synaptic vesicles with active zones at the cytoplasmic surface of the nerve terminal. 

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