The discoidin domain receptor DDR2 is a receptor for type X collagen

• Published in: Matrix biology 2006-08, Vol.25 (6), p.355-364
• Main Authors: Leitinger, Birgit, Kwan, Alvin P.L.
• Format: Article
• Language: English
• Subjects: Animals; Cartilage - metabolism; Cell–extracellular matrix interaction; Chick Embryo; Chondrocytes - metabolism; Collagen - chemistry; Collagen receptor; Collagen Type X - chemistry; Collagen Type X - metabolism; Collagen X; Discoidin domain receptor; Discoidin Domain Receptors; Dose-Response Relationship, Drug; Extracellular Matrix - metabolism; Humans; Mice; Mice, Inbred BALB C; Phosphorylation; Protein Binding; Receptor Protein-Tyrosine Kinases - chemistry; Receptor Protein-Tyrosine Kinases - metabolism; Receptor Protein-Tyrosine Kinases - physiology; Receptors, Mitogen - chemistry; Receptors, Mitogen - metabolism; Receptors, Mitogen - physiology; Recombinant Proteins - chemistry
• ISSN: 0945-053X; 1569-1802
• DOI: 10.1016/j.matbio.2006.05.006

During endochondral ossification, collagen X is deposited in the hypertrophic zone of the growth plate. Our previous results have shown that collagen X is capable of interacting directly with chondrocytes, primarily via integrin α2β1. In this study, we determined whether collagen X could also interact with the non-integrin collagen receptors, discoidin domain receptors (DDRs), DDR1 or DDR2. The widely expressed DDRs are receptor tyrosine kinases that are activated by a number of different collagen types. Collagen X was found to be a much better ligand for DDR2 than for DDR1. Collagen X bound to the DDR2 extracellular domain with high affinity and stimulated DDR2 autophosphorylation, the first step in transmembrane signalling. Expression of DDR2 in the epiphyseal plate was confirmed by RT-PCR and immunohistochemistry. The spatial expression of DDR2 in the hypertrophic zone of the growth plate is consistent with a physiological interaction of DDR2 with collagen X. Surprisingly, the discoidin domain of DDR2, which fully contains the binding sites for the fibrillar collagens I and II, was not sufficient for collagen X binding. The nature of the DDR2 binding site(s) within collagen X was further analysed. In addition to a collagenous domain, collagen X contains a C-terminal NC1 domain. DDR2 was found to recognise the triple-helical region of collagen X as well as the NC1 domain. Binding to the collagenous region was dependent on the triple-helical conformation. DDR2 autophosphorylation was induced by the collagen X triple-helical region but not the NC1 domain, indicating that the triple-helical region of collagen X contains a specific DDR2 binding site that is capable of receptor activation. Our study is the first to describe a non-fibrillar collagen ligand for DDR2 and will form the basis for further studies into the biological function of collagen X during endochondral ossification.