Fibronectin and heparin binding domains of latent TGF-β binding protein (LTBP)-4 mediate matrix targeting and cell adhesion
| Autor: | Anna K. Kantola, Katri Koli, Jorma Keski-Oja |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
CHO Cells
Cell Communication Fibroblast growth factor Models Biological Extracellular matrix Mice 03 medical and health sciences Cricetulus 0302 clinical medicine Cricetinae Cell Adhesion medicine Animals Humans Binding site Fibroblast Cell adhesion Cells Cultured 030304 developmental biology 0303 health sciences Binding Sites biology Heparin Binding protein Cell Biology Adhesion Fibroblasts Extracellular Matrix Fibronectins Protein Structure Tertiary Cell biology Fibronectin medicine.anatomical_structure Latent TGF-beta Binding Proteins Mink 030220 oncology & carcinogenesis biology.protein Protein Binding |
| Zdroj: | Experimental Cell Research. 314:2488-2500 |
| ISSN: | 0014-4827 |
| Popis: | Latent transforming growth factor (TGF)-β binding proteins are extracellular matrix (ECM) proteins involved in the regulation of TGF-β sequestration and activation. In this study, we have identified binding domains in LTBP-4, which mediate matrix targeting and cell adhesion. LTBP-4 was found to possess heparin binding activity, especially in its N-terminal region. The C-terminal domain of LTBP-4 supported fibroblast adhesion, a property reduced by soluble heparin. In addition, we found that LTBP-4 binds directly to fibronectin (FN), which was indispensable for the matrix assembly of LTBP-4. The FN binding sites were also located in the N-terminal region. Interestingly, heparin was able to reduce the binding of LTBP-4 to FN. In fibroblast cultures, LTBP-4 colocalized first with FN and subsequently with fibrillin-1, pointing to a role for FN in the early assembly of LTBP-4. In FN −/− fibroblasts, LTBP-mediated ECM targeting was disturbed, resulting in increased TGF-β activity. These results revealed new molecular interactions which are evidently important for the ECM targeting, but which also are evidence of novel functions for LTBP-4 as an adhesion molecule. |
| Databáze: | OpenAIRE |
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