Endocytosis Cholera toxin

Cholera Toxin Subunit B. a marker for caveolae-dependent endocytosis. partly co-localizes with liposomal FITC>dextran indicating that pH-sensitive liposomes are taken up-at least to a certain extend— via caveotae pathway... 

The apical clathrin-independent pathway is selectively stimulated by reagents that raise intracellular cAMP, such as mastoparan, fluoride, or cholera toxin. Apical endocytosis is also stimulated by brefeldin A (BFA) (106) or by PMA. For an excellent review on transcytosis, see Tuma and Hubbard (138). 

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. 

Lipid raft domains of plasma membranes are enriched in cholesterol and sphingolipids. As a consequence, compounds that extract or sequester cholesterol, such as fS-cyclodextrins, nystatin, and filipin, can block selectively endocytosis of cholera toxin, GPI-linked proteins, and other receptors that associate with lipid rafts and caveolae. However, cholesterol is also critical for CME, secretion of proteins, and the actin network. Therefore, conditions designed to affect selectively raft-mediated endocytosis by perturbing cholesterol levels must be carefully controlled to avoid disrupting other mechanisms of endocytosis (40). 

It should also be pointed out in this connection that clathrin-coated pits are not the only route of endocytosis into eukaryotic cells. There are also other coat proteins. Studies of protein toxins have shown that some (e.g. cholera toxin) enter the cell without the aid of clathrin. 

Joseph KC, Kim SU, Strieber A, et al. (1978) Endocytosis of cholera toxin into neuronal GERL. In Proc. Natl. Acad. Sci. USA 75 2815—2819. 

The damaging effects of many bacterial toxins occur only after endocytosis into the host cell, a process that is initiated by lectin-ligand binding. The binding of the B subunit of cholera toxin (Special Interest Box 5.1) to a glycolipid on the surface of intestinal cells results in the uptake of the toxic A subunit. Once the A subunit is internalized it proceeds to disrupt the mechanism that regulates chloride transport, a process that results in a life-threatening diarrhea. 

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. 

Several ceUular toxins of the AB type have been shown to enter the cell by endocytosis, followed by intracellular transport to the Golgi compartment and the ER (Hazes and Read, 1997). Among this subgroup are the cholera... 

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