Membrane traffic and the cellular uptake of cholera toxin

In nature, cholera toxin (CT) and the structurally related E. coli heat lab ile toxin type I (LTI) must breech the epithelial barrier of the intestine to cause the massive diarrhea seen in cholera. This requires endocytosis of toxin-receptor complexes into the apical endosome, retrograde transport in to Golgi cisternae or endoplasmic reticulum (ER), and finally transport of toxin across the cell to its site of action on the basolateral membrane. Ta rgeting into this pathway depends on toxin binding ganglioside GM1 and asso ciation with caveolae-like membrane domains. Thus to cause disease, both CT and LTI co-opt the molecular machinery used by the host cell to sort, move , and organize their cellular membranes and substituent components. (C) 199 9 Elsevier Science B.V. All rights reserved.