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.
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.
Fantini
J
J
Laboratoire de Biochimie et Biologie de la Nutrition, ESA-CNRS 6033, Faculté des Sciences de St Jérome, Marseille, France. JACQUES.FANTINI@LBBN.u-3mrs.fr
Maresca
M
M
Hammache
D
D
Yahi
N
N
Delézay
O
O
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002772:Cholera Toxin / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology / Q000821:virology; D005677:G(M1) Ganglioside / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D005699:Galactosylceramides / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006028:Glycosphingolipids / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007422:Intestines / Q000166:cytology / Q000382:microbiology* / Q000821:virology*; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D010695:Phlorhizin / Q000494:pharmacology; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism
D005699:Galactosylceramides; D006028:Glycosphingolipids; D015699:HIV Envelope Protein gp120; D005677:G(M1) Ganglioside; D002772:Cholera Toxin; D012964:Sodium; D010695:Phlorhizin; D019204:GTP-Binding Proteins; D005947:Glucose; D002118:Calcium