Glycosphingolipid (GSL) microdomains as attachment platforms for host pathogens and their toxins on intestinal epithelial cells: Activation of signaltransduction pathways and perturbations of intestinal absorption and secretion

Glycosphingolipid (GSL)-enriched microdomains are used as cellular binding sites for various pathogens including viruses and bacteria. These attachmen t platforms are specifically associated with transducer molecules, so that the binding of host pathogens (or their toxins) to the cell surface may res ult in the activation of signal transduction pathways. In the intestinal ep ithelium, such pathogen-induced dysregulations of signal transduction can e licit a severe impairment of enterocytic functions. In this study, we demon strate that the interaction of a bacterial toxin (cholera toxin) and a vira l envelope glycoprotein (HIV-1 gp120) with the apical plasma membrane of in testinal cells is mediated by GSL-enriched microdomains that are associated with G regulatory proteins. These microbial proteins induce a GSL-dependen t increase of intestinal fluid secretion by two mechanisms: activation of c hloride secretion and inhibition of Na+-dependent glucose absorption. Taken together, these data support the view that GSL-enriched microdomains in th e apical plasma membrane of enterocytes are involved in the regulation of i ntestinal functions.