ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation
| Autor: | Karina Reiss, Bart De Strooper, Julian Buchholz, Erhardt Proksch, Dieter H. Hartmann, Felix Scholz, Thorsten Maretzky, Paul Saftig, Andreas Ludwig |
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| Rok vydání: | 2005 |
| Předmět: |
Keratinocytes
ADAM10 Blotting Western Genetic Vectors Down-Regulation Biology Transfection ADAM10 Protein Mice Cell Movement Cell Line Tumor Disintegrin Cell Adhesion Animals Humans Cyclin D1 Cell adhesion beta Catenin Cell Proliferation Wound Healing Multidisciplinary Cell growth Cadherin Membrane Proteins Metalloendopeptidases Cell migration Epithelial Cells Fibroblasts Biological Sciences Cadherins Embryo Mammalian Molecular biology Cell biology Protein Structure Tertiary ADAM Proteins Cytoskeletal Proteins Protein Transport Ectodomain Epithelial cell-cell adhesion biology.protein Trans-Activators RNA Interference Amyloid Precursor Protein Secretases Protein Binding Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 102(26) |
| ISSN: | 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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