Fibrillin assembly requires fibronectin
| Autor: | Laetitia Sabatier, Daliang Chen, Douglas S. Annis, Dirk Hubmacher, Christine Fagotto-Kaufmann, Deane F. Mosher, Marc D. McKee, Dieter P. Reinhardt |
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| Rok vydání: | 2008 |
| Předmět: |
musculoskeletal diseases
Male congenital hereditary and neonatal diseases and abnormalities Fibrillin-2 Fibrillin-1 Molecular Sequence Data macromolecular substances Biology Fibril Fibrillins Extracellular matrix Immunolabeling Fibrillin Microfibrils Protein Interaction Mapping Humans Amino Acid Sequence skin and connective tissue diseases Protein Structure Quaternary Molecular Biology Fluorescent Dyes Binding Sites integumentary system Microfilament Proteins Cell Biology Dermis Articles Fibroblasts Recombinant Proteins Extracellular Matrix Fibronectins Fibronectin Molecular Weight Protein Transport Biochemistry Child Preschool biology.protein Biophysics Gelatin Collagen Peptides Fibrillin Protein Binding |
| Zdroj: | Molecular biology of the cell. 20(3) |
| ISSN: | 1939-4586 |
| Popis: | Fibrillins constitute the major backbone of multifunctional microfibrils in elastic and nonelastic extracellular matrices. Proper assembly mechanisms are central to the formation and function of these microfibrils, and their properties are often compromised in pathological circumstances such as in Marfan syndrome and in other fibrillinopathies. Here, we have used human dermal fibroblasts to analyze the assembly of fibrillin-1 in dependence of other matrix-forming proteins. siRNA knockdown experiments demonstrated that the assembly of fibrillin-1 is strictly dependent on the presence of extracellular fibronectin fibrils. Immunolabeling performed at the light and electron microscopic level showed colocalization of fibrillin-1 with fibronectin fibrils at the early stages of the assembly process. Protein-binding assays demonstrated interactions of fibronectin with a C-terminal region of fibrillin-1, -2, and -3 and with an N-terminal region of fibrillin-1. The C-terminal half of fibrillin-2 and -3 had propensities to multimerize, as has been previously shown for fibrillin-1. The C-terminal of all three fibrillins interacted strongly with fibronectin as multimers, but not as monomers. Mapping studies revealed that the major binding interaction between fibrillins and fibronectin involves the collagen/gelatin-binding region between domains FNI6and FNI9. |
| Databáze: | OpenAIRE |
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