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. 1999 Aug 1;341(Pt 3):555–561.

The cartilage-specific (V+C)- fibronectin isoform exists primarily in homodimeric and monomeric configurations.

N Burton-Wurster 1, R Gendelman 1, H Chen 1, D N Gu 1, J W Tetreault 1, G Lust 1, J E Schwarzbauer 1, J N MacLeod 1
PMCID: PMC1220391  PMID: 10417317

Abstract

Fibronectin is an extracellular-matrix glycoprotein encoded by a single gene, but with significant protein heterogeneity introduced through alternative RNA splicing and post-translational modifications. The (V+C)(-) splice variant, in which nucleotides encoding protein segments III-15 and I-10 are deleted along with the entire variable region, is unique in that expression is restricted to cartilaginous tissues. All known fibronectin splice variants retain the two C-terminal cysteine residues essential for dimerization, but cellular and/or structural constraints appear to influence homo- and heterodimerization patterns. Dimerization patterns of the (V+C)(-) isoform were studied under native conditions within canine articular cartilage and experimentally in COS-7, NIH-3T3 and CHO-K1 cell cultures. In all systems, (V+C)(-) fibronectin secretion was predominantly in a homodimeric configuration. Lower levels of (V+C)(-) monomers were also present. Heterodimers of (V+C)(-) with V(+),C(+) (V120) isoforms were not detected. Heterodimers of (V+C)(-) with V(-),C(+) (V0) subunits were detected only at low levels. Functional properties may differ significantly among monomers, homodimers and heterodimers. The unique dimerization pattern of (V+C)(-) fibronectin is consistent with this isoform having specialized functional properties in situ that are important for either the structural organization and biomechanical properties of cartilage matrix or regulation of a chondrocytic phenotype.

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Selected References

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  1. Burton-Wurster N., Borden C., Lust G., Macleod J. N. Expression of the (V+C)- fibronectin isoform is tightly linked to the presence of a cartilaginous matrix. Matrix Biol. 1998 Jul;17(3):193–203. doi: 10.1016/s0945-053x(98)90058-0. [DOI] [PubMed] [Google Scholar]
  2. Burton-Wurster N., Lust G. Fibronectin and proteoglycan synthesis in long term cultures of cartilage explants in Ham's F12 supplemented with insulin and calcium: effects of the addition of TGF-beta. Arch Biochem Biophys. 1990 Nov 15;283(1):27–33. doi: 10.1016/0003-9861(90)90607-z. [DOI] [PubMed] [Google Scholar]
  3. Burton-Wurster N., Lust G., Macleod J. N. Cartilage fibronectin isoforms: in search of functions for a special population of matrix glycoproteins. Matrix Biol. 1997 Mar;15(7):441–454. doi: 10.1016/s0945-053x(97)90018-4. [DOI] [PubMed] [Google Scholar]
  4. Burton-Wurster N., Lust G. Molecular and immunologic differences in canine fibronectins from articular cartilage and plasma. Arch Biochem Biophys. 1989 Feb 15;269(1):32–45. doi: 10.1016/0003-9861(89)90084-2. [DOI] [PubMed] [Google Scholar]
  5. Burton-Wurster N., Zhang D. W., Lust G. Accumulation of fibronectin in articular cartilage explants cultured with TGF beta 1 and fucoidan. Arch Biochem Biophys. 1995 Jan 10;316(1):452–460. doi: 10.1006/abbi.1995.1060. [DOI] [PubMed] [Google Scholar]
  6. Castle A. M., Schwarzbauer J. E., Wright R. L., Castle J. D. Differential targeting of recombinant fibronectins in AtT-20 cells based on their efficiency of aggregation. J Cell Sci. 1995 Dec;108(Pt 12):3827–3837. doi: 10.1242/jcs.108.12.3827. [DOI] [PubMed] [Google Scholar]
  7. Choi M. G., Hynes R. O. Biosynthesis and processing of fibronectin in NIL.8 hamster cells. J Biol Chem. 1979 Dec 10;254(23):12050–12055. [PubMed] [Google Scholar]
  8. Gorman C., Padmanabhan R., Howard B. H. High efficiency DNA-mediated transformation of primate cells. Science. 1983 Aug 5;221(4610):551–553. doi: 10.1126/science.6306768. [DOI] [PubMed] [Google Scholar]
  9. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  10. Guan J. L., Trevithick J. E., Hynes R. O. Retroviral expression of alternatively spliced forms of rat fibronectin. J Cell Biol. 1990 Mar;110(3):833–847. doi: 10.1083/jcb.110.3.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  12. MacLeod J. N., Burton-Wurster N., Gu D. N., Lust G. Fibronectin mRNA splice variant in articular cartilage lacks bases encoding the V, III-15, and I-10 protein segments. J Biol Chem. 1996 Aug 2;271(31):18954–18960. doi: 10.1074/jbc.271.31.18954. [DOI] [PubMed] [Google Scholar]
  13. Nixon A. J., Lust G., Vernier-Singer M. Isolation, propagation, and cryopreservation of equine articular chondrocytes. Am J Vet Res. 1992 Dec;53(12):2364–2370. [PubMed] [Google Scholar]
  14. Ruoslahti E., Hayman E. G., Pierschbacher M., Engvall E. Fibronectin: purification, immunochemical properties, and biological activities. Methods Enzymol. 1982;82(Pt A):803–831. doi: 10.1016/0076-6879(82)82103-4. [DOI] [PubMed] [Google Scholar]
  15. Schwarzbauer J. E. Alternative splicing of fibronectin: three variants, three functions. Bioessays. 1991 Oct;13(10):527–533. doi: 10.1002/bies.950131006. [DOI] [PubMed] [Google Scholar]
  16. Schwarzbauer J. E., Mulligan R. C., Hynes R. O. Efficient and stable expression of recombinant fibronectin polypeptides. Proc Natl Acad Sci U S A. 1987 Feb;84(3):754–758. doi: 10.1073/pnas.84.3.754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schwarzbauer J. E., Spencer C. S., Wilson C. L. Selective secretion of alternatively spliced fibronectin variants. J Cell Biol. 1989 Dec;109(6 Pt 2):3445–3453. doi: 10.1083/jcb.109.6.3445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sottile J., Mosher D. F. Assembly of fibronectin molecules with mutations or deletions of the carboxyl-terminal type I modules. Biochemistry. 1993 Feb 16;32(6):1641–1647. doi: 10.1021/bi00057a031. [DOI] [PubMed] [Google Scholar]
  19. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Zhang D. W., Burton-Wurster N., Lust G. Alternative splicing of ED-A and ED-B sequences of fibronectin pre-mRNA differs in chondrocytes from different cartilaginous tissues and can be modulated by biological factors. J Biol Chem. 1995 Jan 27;270(4):1817–1822. doi: 10.1074/jbc.270.4.1817. [DOI] [PubMed] [Google Scholar]

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