Heterogeneity of detergent-insoluble membranes from human intestine containing caveolin-1 and ganglioside GM1

被引:37
作者
Badizadegan, K
Dickinson, BL
Wheeler, HE
Blumberg, RS
Holmes, RK
Lencer, WI
机构
[1] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
[3] Childrens Hosp, Combined Program Pediat Gastroenterol, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA
[5] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA
[6] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[7] Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA
[8] Harvard Digest Dis Ctr, Boston, MA 02115 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2000年 / 278卷 / 06期
关键词
caveolae; cholera toxin; toxigenic diarrhea;
D O I
10.1152/ajpgi.2000.278.6.G895
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:G895 / G904
页数:10
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