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.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Wu S,Rhee KJ,Zhang M,Franco A,Sears CLdoi
10.1242/jcs.03455subject
Has Abstractpub_date
2007-06-01 00:00:00pages
1944-52issue
Pt 11eissn
0021-9533issn
1477-9137pii
jcs.03455journal_volume
120pub_type
杂志文章abstract：:We first identified Bves (blood vessel/epicardial substance) as a transmembrane protein that localized to the lateral compartment of the epithelial epicardium. Bves traffics to sites of cell-cell contact in cultured epicardial cells and promotes adhesion following transfection into non-adherent fibroblastic L-cells, r...
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journal_title：Journal of cell science
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journal_title：Journal of cell science
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journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：
更新日期：2002-06-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1991-02-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1982-10-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-06-01 00:00:00
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pub_type： 杂志文章
doi：10.1242/jcs.067447
更新日期：2010-12-15 00:00:00
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更新日期：2012-02-15 00:00:00
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doi：
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doi：
更新日期：1994-11-01 00:00:00
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doi：
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journal_title：Journal of cell science
pub_type： 杂志文章,评审
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更新日期：2002-01-01 00:00:00
