Heterogeneity of detergent-insoluble membranes from human intestine containing caveolin-1 and ganglioside G(M1).
In intestinal epithelia, cholera and related toxins elicit a cAMP-dependent chloride secretory response fundamental to the pathogenesis of toxigenic diarrhea. We recently proposed that specificity of cholera toxin (CT) action in model intestinal epithelia may depend on the toxin's cell surface receptor ganglioside G(M1). Binding G(M1) enabled the toxin to elicit a response, but forcing the toxin to enter the cell by binding the closely related ganglioside G(D1a) rendered the toxin inactive. The specificity of ganglioside function correlated with the ability of G(M1) to partition CT into detergent-insoluble glycosphingolipid-rich membranes (DIGs). To test the biological plausibility of these hypotheses, we examined native human intestinal epithelia. We show that human small intestinal epithelia contain DIGs that distinguish between toxin bound to G(M1) and G(D1a), thus providing a possible mechanism for enterotoxicity associated with CT. We find direct evidence for the presence of caveolin-1 in DIGs from human intestinal epithelia but find that these membranes are heterogeneous and that caveolin-1 is not a structural component of apical membrane DIGs that contain CT.
Badizadegan
K
K
Department of Pathology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. badizadegan@hub.tch.harvard.edu
Dickinson
B L
BL
Wheeler
H E
HE
Blumberg
R S
RS
Holmes
R K
RK
Lencer
W I
WI
D001427:Bacterial Toxins / Q000378:metabolism; D051242:Caveolin 1; D022461:Caveolins; D016764:Cell Polarity; D002772:Cholera Toxin / Q000378:metabolism; D046508:Culture Techniques; D003902:Detergents / Q000494:pharmacology*; D004768:Enterotoxins / Q000378:metabolism; D029968:Escherichia coli Proteins; D005677:G(M1) Ganglioside / Q000378:metabolism*; D006028:Glycosphingolipids / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D012995:Solubility
D001427:Bacterial Toxins; C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D003902:Detergents; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D006028:Glycosphingolipids; D008565:Membrane Proteins; D005677:G(M1) Ganglioside; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli