Dataset Information

Bacteroides fragilis toxin stimulates intestinal epithelial cell shedding and gamma-secretase-dependent E-cadherin cleavage.

ABSTRACT: Enterotoxigenic Bacteroides fragilis - organisms that live in the colon - secrete a metalloprotease toxin, B. fragilis toxin. This toxin binds to a specific intestinal epithelial cell receptor and stimulates cell proliferation, which is dependent, in part, on E-cadherin degradation and beta-catenin-T-cell-factor nuclear signaling. Gamma-secretase (or presenilin-1) is an intramembrane cleaving protease and is a positive regulator of E-cadherin cleavage and a negative regulator of beta-catenin signaling. Here we examine the mechanistic details of toxin-initiated E-cadherin cleavage. B. fragilis toxin stimulated shedding of cell membrane proteins, including the 80 kDa E-cadherin ectodomain. Shedding of this domain required biologically active toxin and was not mediated by MMP-7, ADAM10 or ADAM17. Inhibition of gamma-secretase blocked toxin-induced proteolysis of the 33 kDa intracellular E-cadherin domain causing cell membrane retention of a distinct beta-catenin pool without diminishing toxin-induced cell proliferation. Unexpectedly, gamma-secretase positively regulated basal cell proliferation dependent on the beta-catenin-T-cell-factor complex. We conclude that toxin induces step-wise cleavage of E-cadherin, which is dependent on toxin metalloprotease and gamma-secretase. Our results suggest that differentially regulated beta-catenin pools associate with the E-cadherin-gamma-secretase adherens junction complex; one pool regulated by gamma-secretase is important to intestinal epithelial cell homeostasis.

SUBMITTER: Wu S

PROVIDER: S-EPMC3056613 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

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Bacteroides fragilis toxin stimulates intestinal epithelial cell shedding and gamma-secretase-dependent E-cadherin cleavage.

Wu Shaoguang S Rhee Ki-Jong KJ Zhang Ming M Franco Augusto A Sears Cynthia L CL

Journal of cell science 20070515 Pt 11

Enterotoxigenic Bacteroides fragilis - organisms that live in the colon - secrete a metalloprotease toxin, B. fragilis toxin. This toxin binds to a specific intestinal epithelial cell receptor and stimulates cell proliferation, which is dependent, in part, on E-cadherin degradation and beta-catenin-T-cell-factor nuclear signaling. Gamma-secretase (or presenilin-1) is an intramembrane cleaving protease and is a positive regulator of E-cadherin cleavage and a negative regulator of beta-catenin sig ...[more]

PMID: 17504810

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Dataset Information

Bacteroides fragilis toxin stimulates intestinal epithelial cell shedding and gamma-secretase-dependent E-cadherin cleavage.

Publications

Bacteroides fragilis toxin stimulates intestinal epithelial cell shedding and gamma-secretase-dependent E-cadherin cleavage.

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