The Cysteine-Rich Domain of Human Adam 12 Supports Cell Adhesion through Syndecans and Triggers Signaling Events That Lead to β1 Integrin–Dependent Cell Spreading
Autor: | Reidar Albrechtsen, Kousuke Iba, J K Langford, Ralph D. Sanderson, Brent Gilpin, Camilla Fröhlich, Ulla M. Wewer, K Ishiguro, Frosty Loechel, A Zolkiewska, Cord Brakebusch, T Kojima, Reinhard Fässler, Wei Liu |
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Rok vydání: | 2000 |
Předmět: |
0303 health sciences
biology Cell Cell Biology ADAM Proteins Molecular biology 3. Good health Syndecan 1 carbohydrates (lipids) Focal adhesion 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure 030220 oncology & carcinogenesis Disintegrin biology.protein medicine Signal transduction Cell adhesion Cytoskeleton 030304 developmental biology |
Zdroj: | Journal of Cell Biology. 149:1143-1156 |
ISSN: | 1540-8140 0021-9525 |
Popis: | The ADAMs (a disintegrin and metalloprotease) family of proteins is involved in a variety of cellular interactions, including cell adhesion and ecto- domain shedding. Here we show that ADAM 12 binds to cell surface syndecans. Three forms of recombinant ADAM 12 were used in these experiments: the cys-teine-rich domain made in Escherichia coli (rADAM 12-cys), the disintegrin-like and cysteine-rich domain made in insect cells (rADAM 12-DC), and full-length human ADAM 12-S tagged with green fluorescent protein made in mammalian cells (rADAM 12-GFP). Mesenchymal cells specifically and in a dose-dependent manner attach to ADAM 12 via members of the syndecan family. After binding to syndecans, mesenchymal cells spread and form focal adhesions and actin stress fibers. Integrin β1 was responsible for cell spreading because function-blocking monoclonal antibodies completely inhibited cell spreading, and chondroblasts lacking β1 integrin attached but did not spread. These data suggest that mesenchymal cells use syndecans as the initial receptor for the ADAM 12 cysteine-rich domain–mediated cell adhesion, and then the β1 integrin to induce cell spreading. Interestingly, carcinoma cells attached but did not spread on ADAM 12. However, spreading could be efficiently induced by the addition of either 1 mM Mn2+ or the β1 integrin–activating monoclonal antibody 12G10, suggesting that in these carcinoma cells, the ADAM 12–syndecan complex fails to modulate the function of β1 integrin. |
Databáze: | OpenAIRE |
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