|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online 15 May 2007
doi: 10.1242/jcs.03455
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research Article |
-secretase-dependent E-cadherin cleavage
1 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
2 Division of Gastroenterology, Department of Medicine, Johns Hopkins University School of Medicine, 1550 Orleans St, CRB2 Bldg Suite 1M.05, Baltimore, MD 21231, USA
* Author for correspondence (e-mail: csears{at}jhmi.edu)
Accepted 10 April 2007
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 
-catenin–T-cell-factor nuclear signaling. 
-Secretase (or presenilin-1) is an intramembrane cleaving protease and is a positive regulator of E-cadherin cleavage and a negative regulator of -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 -secretase blocked toxin-induced proteolysis of the 33 kDa intracellular E-cadherin domain causing cell membrane retention of a distinct -catenin pool without diminishing toxin-induced cell proliferation. Unexpectedly, -secretase positively regulated basal cell proliferation dependent on the -catenin–T-cell-factor complex. We conclude that toxin induces step-wise cleavage of E-cadherin, which is dependent on toxin metalloprotease and -secretase. Our results suggest that differentially regulated -catenin pools associate with the E-cadherin–-secretase adherens junction complex; one pool regulated by -secretase is important to intestinal epithelial cell homeostasis.
Key words: Bacteroides fragilis, Bacteroides fragilis toxin, Metalloproteases, E-cadherin, ADAM, -secretase
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
Related articles in JCS:
This article has been cited by other articles:
|
|
 |
|
  A M Muise, T D Walters, W K Glowacka, A M Griffiths, B-Y Ngan, H Lan, W Xu, M S Silverberg, and D Rotin Polymorphisms in E-cadherin (CDH1) result in a mis-localised cytoplasmic protein that is associated with Crohn's disease Gut, August 1, 2009; 58(8): 1121 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Sears Enterotoxigenic Bacteroides fragilis: a Rogue among Symbiotes Clin. Microbiol. Rev., April 1, 2009; 22(2): 349 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-J. Rhee, S. Wu, X. Wu, D. L. Huso, B. Karim, A. A. Franco, S. Rabizadeh, J. E. Golub, L. E. Mathews, J. Shin, et al. Induction of Persistent Colitis by a Human Commensal, Enterotoxigenic Bacteroides fragilis, in Wild-Type C57BL/6 Mice Infect. Immun., April 1, 2009; 77(4): 1708 - 1718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Ferber, M. Kajita, A. Wadlow, L. Tobiansky, C. Niessen, H. Ariga, J. Daniel, and Y. Fujita A Role for the Cleaved Cytoplasmic Domain of E-cadherin in the Nucleus J. Biol. Chem., May 9, 2008; 283(19): 12691 - 12700. [Abstract] [Full Text] [PDF]
|
|
