Glycosphingolipid (GSL) microdomains as attachment platforms for host pathogens and their toxins on intestinal epithelial cells: Activation of signal transduction pathways and perturbations of intestinal absorption and secretion |
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Authors: | Jacques Fantini Marc Maresca Djilali Hammache Nouara Yahi Olivier Delézay |
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Institution: | (1) Laboratoire de Biochimie et Biologie de la Nutrition, ESA-CNRS 6033, Faculté des Sciences de St Jérôme, 13397 Marseille Cedex 20, France;(2) Laboratoire de Virologie, UF SIDA, Hôpital de la Timone, 13005 Marseille;(3) Faculté de Médecine, GIMAP, 42023 St Etienne Cedex 2, France |
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Abstract: | Glycosphingolipid (GSL)-enriched microdomains are used as cellular binding sites for various pathogens including viruses and bacteria. These attachment platforms are specifically associated with transducer molecules, so that the binding of host pathogens (or their toxins) to the cell surface may result in the activation of signal transduction pathways. In the intestinal epithelium, such pathogen-induced dysregulations of signal transduction can elicit a severe impairment of enterocytic functions. In this study, we demonstrate that the interaction of a bacterial toxin (cholera toxin) and a viral envelope glycoprotein (HIV-1 gp120) with the apical plasma membrane of intestinal cells is mediated by GSL-enriched microdomains that are associated with G regulatory proteins. These microbial proteins induce a GSL-dependent increase of intestinal fluid secretion by two mechanisms: activation of chloride secretion and inhibition of Na+-dependent glucose absorption. Taken together, these data support the view that GSL-enriched microdomains in the apical plasma membrane of enterocytes are involved in the regulation of intestinal functions. |
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Keywords: | glycolipids HIV-1 cholera toxin signal transduction epithelial intestinal cells air-water interface monolayer |
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