ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and Î²-catenin translocation

Thorsten Maretzky; Karina Reiss; Andreas Ludwig; Julian Buchholz; Felix Scholz; Erhardt Proksch; Bart de Strooper; Dieter Hartmann; Paul Saftig

doi:10.1073/pnas.0500918102

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ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and Î²-catenin translocation

Journal article

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ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and Î²-catenin translocation

Thorsten Maretzky, Karina Reiss, Andreas Ludwig, Julian Buchholz, Felix Scholz, Erhardt Proksch, Bart de Strooper, Dieter Hartmann and Paul Saftig

Proceedings of the National Academy of Sciences - PNAS, Vol.102(26), pp.9182-9187

06/28/2005

DOI: 10.1073/pnas.0500918102

PMCID: PMC1166595

PMID: 15958533

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Abstract

E-cadherin controls a wide array of cellular behaviors, including cell-cell adhesion, differentiation, and tissue development. We show here that E-cadherin is cleaved specifically by ADAM (a disintegrin and metalloprotease) 10 in its ectodomain. Analysis of ADAM10-deficient fibroblasts, inhibitor studies, and RNA interference-mediated down-regulation of ADAM10 demonstrated that ADAM10 is responsible not only for the constitutive shedding but also for the regulated shedding of this adhesion molecule in fibroblasts and keratinocytes. ADAM10-mediated E-cadherin shedding affects epithelial cell-cell adhesion as well as cell migration. Furthermore, the shedding of E-cadherin by ADAM10 modulates the β-catenin subcellular localization and downstream signaling. ADAM10 overexpression in epithelial cells increased the expression of the β-catenin downstream gene cyclin D1 dose-dependently and enhanced cell proliferation. In ADAM10-deficient mouse embryos, the C-terminal E-cadherin fragment is not generated, and the full-length protein accumulates, highlighting the in vivo relevance for ADAM10 in E-cadherin shedding. Our data strongly suggest that this protease constitutes a major regulatory element for the multiple functions of E-cadherin under physiological as well as pathological conditions.

metalloproteinases

Biological Sciences

ADAM

cadherin

shedding

Details

Title: Subtitle: ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and Î²-catenin translocation
Creators: Thorsten Maretzky - Biochemical Institute and
Karina Reiss - Biochemical Institute and
Andreas Ludwig - Biochemical Institute and
Julian Buchholz - Biochemical Institute and
Felix Scholz - Biochemical Institute and
Erhardt Proksch - Biochemical Institute and
Bart de Strooper - Biochemical Institute and
Dieter Hartmann - Biochemical Institute and
Paul Saftig - Biochemical Institute and
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.102(26), pp.9182-9187
DOI: 10.1073/pnas.0500918102
PMID: 15958533
PMCID: PMC1166595
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 06/28/2005
Academic Unit: Internal Medicine
Record Identifier: 9984094341802771

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