Membrane traffic and the cellular uptake of cholera toxin.
In nature, cholera toxin (CT) and the structurally related E. coli heat labile 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 into Golgi cisternae or endoplasmic reticulum (ER), and finally transport of toxin across the cell to its site of action on the basolateral membrane. Targeting into this pathway depends on toxin binding ganglioside GM1 and association 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.
Combined Program in Pediatric Gastroenterology, Children's Hospital, Harvard Medical School, Harvard Digestive Diseases Center, Boston, MA, USA. lencer@a1.tch.harvard.edu
W I
WI
Lencer
T R
TR
Hirst
R K
RK
Holmes
D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D002772:Cholera Toxin / Q000737:chemistry / Q000378:metabolism*; D004705:Endocytosis; D004768:Enterotoxins / Q000737:chemistry / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D029968:Escherichia coli Proteins; D005677:G(M1) Ganglioside / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D005677:G(M1) Ganglioside; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli