Cartilage oligomeric matrix protein promotes cell attachment via two independent mechanisms involving CD47 and αVβ3 integrin
- 243 Downloads
Cartilage oligomeric matrix protein (COMP) is a pentameric ~524 kDa multidomain extracellular matrix protein and is the fifth member of the thrombospondin family. COMP is abundantly expressed in proliferating and hypertrophic chondrocytes of the growth plate, articular cartilage, synovium, tendon, and ligament. The spatial localization of COMP highlights its importance in the phenotypes of pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), COMP disorders that are characterized by disproportionate short stature, brachydactyly, scoliosis, early-onset osteoarthritis, and joint hypermobility. In this study, the role of COMP in ligament was investigated with a series of cell attachment assays using ligament cells binding to COMP. A dose-dependent cell attachment activity was found, which was inhibited by a peptide containing the SFYVVMWK amino acid sequence derived from the globular C-terminal domain of COMP. This activity was independent of the recently described RGD-dependent attachment activity. Function-blocking antibodies to CD47 and αVβ3 integrin reduced cell attachment to COMP, implicating the participation of these cell surface molecules in COMP cell binding. Immunofluorescence studies showed that cell attachment to COMP induced the formation of lamellae containing F-actin microspikes associated with fascin. We propose that COMP promotes cell attachment via two independent mechanisms involving cell surface CD47 and αVβ3 integrin and that a consequence of cell attachment to COMP is the specific induction of fascin-stabilized actin microspikes.
KeywordsCOMP Extracellular matrix Cell adhesion Signaling Actin cytoskeleton
This study was supported in part by grants from the National Institutes of Health (AR493139 and HD22657 (DHC) and the Shriners Hospitals for Children (WAH). Daniel Cohn is a Winnick Family Clinical Research Scholar supported by the General Clinical Research Center at Cedars-Sinai under NCRR grant M01-RR00425. Paul Holden was a recipient of a Shriners Research Fellowship Award. We thank Deborah Krakow for assistance with obtaining cartilage samples, Vincent Funari for help with statistical analysis, Vladimir Vilim for COMP monoclonal antibodies, and MaryAnn Weiss and David Eyre for analyzing COMP purity by mass spectrometry.
- 13.Cohn DH (2003) COMP and pseudoachondroplasia. In: Epstein CJ, Erickson RP, Wynshaw-Boris A (eds) Inborn errors of development. Oxford University Press, New York, pp 970–976Google Scholar
- 16.Kennedy J, Jackson GC, Barker FS, Nundlall S, Bella J et al (2005) Novel and recurrent mutations in the C-terminal domain of COMP cluster in two distinct regions and result in a spectrum of phenotypes within the pseudoachondroplasia—multiple epiphyseal dysplasia disease group. Hum Mutat 25:593–594CrossRefPubMedGoogle Scholar
- 37.Lu X, Davies J, Lu D, Xia M, Wattam B, Shang D, Sun Y, Scully M, Kakkar V (2006) The effect of the single substitution of arginine within the RGD tripeptide motif of a modified neurotoxin dendroaspin on its activity of platelet aggregation and cell adhesion. Cell Commun Adhes 13:171–183CrossRefPubMedGoogle Scholar