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

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

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

Shaoguang Wu,Ki-Jong Rhee,Ming Zhang,Augusto Franco,Cynthia L Sears,Shaoguang Wu,Ki-Jong Rhee,Ming Zhang,Augusto Franco,Cynthia L Sears,

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.

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

S Wu,KJ Rhee,M Zhang,A Franco,CL Sears,S Wu,KJ Rhee,M Zhang,A Franco,CL Sears,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: molecular conformation: protein conformation: protein structure, tertiary research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: molecular conformation: protein conformation: protein structure, tertiary research

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

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of cell science

VOLUME: 120

Page Numbers: 1944-52

Journal Abbreviation: J. Cell. Sci.

ISSN: 0021-9533

DAY: 15

MONTH: 05

YEAR: 2007

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 52457

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

KEYWORDS: Protein Structure, Tertiary

MESH TERMS: drug effects

Chemical & Substance for Abstract: Bacteroides fragilis toxin stimulates intestinal epithelial cell shedding and gamma-secretase-dependent E-cadherin cleavage. Information

Substance Name: Metalloendopeptidases

Registry Number: EC 3.4.24.-

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

AFFILIATION: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, 1550 Orleans St, CRB2 Bldg Suite 1M.05, Baltimore, MD 21231, USA.

Country: England

AGENCY: United States NIDDK

GRANT: R24 DK 64388

ACRONYM: DK

MEDLINETA: J Cell Sci

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