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PMID:19900459

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Citation

Flynn, LA, Blissett, AR, Calomeni, EP and Agarwal, G (2010) Inhibition of collagen fibrillogenesis by cells expressing soluble extracellular domains of DDR1 and DDR2. J. Mol. Biol. 395:533-43

Abstract

Collagen fiber assembly affects many physiological processes and is tightly controlled by collagen-binding proteins. However, to what extent membrane-bound versus cell-secreted collagen-binding proteins affect collagen fibrillogenesis is not well understood. In our previous studies, we had demonstrated that the membrane-anchored extracellular domain (ECD) of the collagen receptor discoidin domain receptor 2 (DDR2) inhibits fibrillogenesis of collagen endogenously secreted by the cells. These results led to a novel functional role of the DDR2 ECD. However, since soluble forms of DDR1 and DDR2 containing its ECD are known to naturally exist in the extracellular matrix, in this work we investigated if these soluble DDR ECDs may have a functional role in modulating collagen fibrillogenesis. For this purpose, we created mouse osteoblast cell lines stably secreting DDR1 or DDR2 ECD as soluble proteins. Transmission electron microscopy, fluorescence microscopy, and hydroxyproline assays were used to demonstrate that DDR ECD expression reduced the rate and quantity of collagen deposition and induced significant changes in fiber morphology and matrix mineralization. Collectively, our studies advance our understanding of DDR receptors as powerful regulators of collagen deposition in the ECM and elucidate their multifaceted role in ECM remodeling.

Links

PubMed PMC2813395 Online version:10.1016/j.jmb.2009.10.073

Keywords

3T3 Cells; Animals; Base Sequence; Collagen/chemistry; Collagen/metabolism; Collagen/ultrastructure; DNA Primers/genetics; Extracellular Matrix/chemistry; Extracellular Matrix/ultrastructure; Hydroxyproline/chemistry; Kinetics; Mice; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Osteoblasts/metabolism; Osteoblasts/ultrastructure; Protein Multimerization; Protein Structure, Tertiary; Receptor Protein-Tyrosine Kinases/chemistry; Receptor Protein-Tyrosine Kinases/genetics; Receptor Protein-Tyrosine Kinases/metabolism; Receptors, Mitogen/chemistry; Receptors, Mitogen/genetics; Receptors, Mitogen/metabolism; Recombinant Proteins/chemistry; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Transfection

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:DDR2

involved_in

GO:0030199: collagen fibril organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DDR2

involved_in

GO:0031214: biomineral tissue development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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