Floating cholera toxin into epithelial cells: functional association with caveolae-like detergent-insoluble membrane microdomains

In polarized cells, signal transduction by cholera toxin (CT) requires apic al endocytosis and retrograde transport into Golgi cisternae and likely end oplasmic reticulum (ER) (Lencer et al., J. Cell Biol. 131, 951-962 (1995)). We have recently found that the toxin's apical membrane receptor gangliosi de GM1 acts specifically in this signal transduction pathway, likely by cou pling CT with caveolae or caveolae-related membrane domains (lipid rafts) ( Wolf et al., J. Cell Biol. 141, 917-927 (1998)). Work in progress shows tha t 1) cholesterol depletion uncouples the CT-GM1 receptor complex from signa l transduction, a characteristic of lipid rafts; 2) the GM1 acyl chains rat her than the carbohydrate head groups appear to account for the structural basis of ganglioside specificity in toxin trafficking; and 3) intestinal ep ithelial cells obtained from normal adult humans exhibit lipid rafts which differentiate between CT-GM1 and LTIIb-GD1a complexes and which contain cav eolin 1.