Fibronectin: Role in Cell Surface Interactions

  • John R. Couchman
  • Anne Woods


Since the early 1970’s, interest in fibronectin has increased steadily, and there is now a massive literature on the structure and functional attributes of this complex molecule (see reviews 1–3)o Although its absence or depletion from the surface of transformed cells first brought fibronectin to the attention of those interested in tumour formation and invasion,the fact that it has significant roles to play in the adhesion and migration of normal cells has widened the field to include connective tissue, developmental biology and more recently molecular biology. Fibronectin is now the most studied of all connective tissue components and two major attributes make this glycoprotein of particular interest. Firstly, the glycoprotein has the capacity to bind other connective tissue components and cell surfaces through a series of domains joined by more flexible regions1 (Fig. l). The implication of this is that fibronectin is ideally suited for a role in mediating cell attachment (whether eukaryotic or prokar- yotic) to collagenous extracellular matrices. Secondly, the molecule is widespread in vivo, deposited in connective tissues and basement membranes and present in a soluble form in many body fluids including plasma, cerebrospinal and amniotic fluids.1–3


Plasma Fibronectin Heparin Binding Domain Connective Tissue Component Cell Surface Interaction Microfilament Bundle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    K.M. Yamada, Cell surface interactions with extracellular materials, Ann. Rev. Biochem 52:761 (1983).CrossRefGoogle Scholar
  2. 2.
    D.F. Mosher, Physiology of fibronectin, Ann. Rev. Med. 35:561 (1984).CrossRefGoogle Scholar
  3. 3.
    R.O. Hynes, Fibronectin and its relation to cellular structure and behavior, in. “Cell Biology of Extracellular Matrix”, E.D. Hay, ed., Plenum Press, New York (1981).Google Scholar
  4. 4.
    A. Vaheri and D.F. Mosher, High molecular weight cell surface- associated glycoprotein (fibronectin) lost in malignant transformation, Biochim. Biophys. Acta 516:1 (1978).Google Scholar
  5. 5.
    R.O. Hynes and K.M. Yamada, Fibronectins: Multi-functional modular glycoproteins, J. Cell Biol. 95:369 (1982).CrossRefGoogle Scholar
  6. 6.
    E. Engvall, E. Ruoslahti, and E.J. Miller, Affinity of fibronectin to collagens of different genetic types and to fibrinogen, J. Exp. Med. 147:1584 (1978).CrossRefGoogle Scholar
  7. 7.
    F. Jilek and Hc Hormann, Cold-insoluble globulin (fibronectin) IV. Affinity to soluble collagen of various types, Hoppe- Seylerls Z. Physiol. Chem. 359:247 (1978).Google Scholar
  8. 8.
    L.I. Gold, B. Frangione, and E. Pearlstein, Biochemical and immunological characterization of three binding sites on human plasma fibronectin with different affinities for heparin, Biochemistry 22:4113 (1983).CrossRefGoogle Scholar
  9. 9.
    I.V. Ali and R.O. Hynes, Effects of LETS glycoprotein on cell motility, Cell 14:439 (1978).CrossRefGoogle Scholar
  10. 10.
    J.R. Couchman, D.A. Rees, M.R. Green, and C.G. Smith, Fibronectin has a dual role in locomotion and anchorage of primary chick fibroblasts and can promote entry into the division cycle, J. Cell Biol. 93:402 (1982).CrossRefGoogle Scholar
  11. 11.
    G. Froman, L. Switalski, A. Faris, T. Wadstrom, and M. Hook, Binding of E© coli to fibronectin - A mechanism of tissue adherence, J. Biol. Chem. In Press (1985).Google Scholar
  12. 12.
    S.K. Akiyama and M.D. Johnson, Fibronectin in evolution: Presence in invertebrates and isolation from Microciona prolifera, Comp. Biochem. Physiol. B. 76:687 (1983).CrossRefGoogle Scholar
  13. 13.
    J.E. Schwarzbauer, J.W. Tamkun, I.R. Lemischka, and R.O, Hynes, Three different fibronectin mRNAs arise by alternative splicing within the coding region, Cell 35:421 (1983).CrossRefGoogle Scholar
  14. 14.
    A.R. Kornblihtt, K. Vibe-Pedersen, and F.E. Baralle, Human fibronectin: molecular cloning evidence for two mRNA species differing by an internal segment coding for a structural domain, EMBO J. 3:221 (1984).Google Scholar
  15. 15.
    J.W. Tamkun, J.E. Schwarzbauer, and R.O. Hynes, A single rat fibronectin gene generates three different mRNAs by alternative splicing of a complex exon, Proc. Natl. Acad. Sci. U.S.A. 81:5140 (1984).CrossRefGoogle Scholar
  16. 16.
    K. Sekiguchi and S. Hakomori, Functional domain structure of fibronectin, Proc. Natl. Acad. Sci. U.S.A. 77:2661 (1980).CrossRefGoogle Scholar
  17. 17.
    J.R. Couchman, M. Hook, D.A. Rees, and R. Timpl, Adhesion, growth and matrix production by fibroblasts on laminin substrates, J. Cell Biol, 96:177 (1983).CrossRefGoogle Scholar
  18. 18.
    D.M. Scott, J.C. Murray, and M.J. Barnes, Investigation of the attachment of bovine corneal endothelial cells to coll- agens and other components of the subendothelium, Exp. Cell Res, 144:472 (1983).CrossRefGoogle Scholar
  19. 19.
    M. Hook, K. Rubin, A. Oldberg, B. Obrink, and A. Vaheri, Cold-insoluble globulin mediates the adhesion of rat liver cells to plastic petri dishes, Biochem. Biophys. Res. Commun. 79:726 (1977).CrossRefGoogle Scholar
  20. 20.
    R.A. Badley, J.R. Couchman, and D.A. Rees, Comparison of the cell cytoskeleton in migratory and stationary chick fibroblasts, J. Muscle Res. Cell Motility 1:5 (1980).CrossRefGoogle Scholar
  21. 21.
    J.R. Couchman, M. Lenn, and D.A. Rees, Coupling of cytoskeleton functions for fibroblast locomotion, Eur. J. Cell Biol. In Press (1985).Google Scholar
  22. 22.
    R.J. Beyth and L.A. Culp, Complementary adhesive responses of human skin fibroblasts to the cell-binding domain of fibronectin and the heparan sulfate-binding protein, platelet factor-4, Exp. Cell Res. 155:537 (1984).CrossRefGoogle Scholar
  23. 23.
    J.E. Doran, A.R. Mansberger, and A.C. Pease, Cold-insoluble globulin-enhanced phagocytosis of gelatinized targets by macrophage monolayers: A model system, J. Retic. Soc. 27:471 (1980).Google Scholar
  24. 24.
    F.A. Blumenstock, T.M. Saba, P. Weber, and R. Laffin, Biochemical and immunological characterization of human opsonic «2 SB glycoprotein: Its identity with cold- insoluble globulin, J. Biol. Chem. 253:4287 (1978).Google Scholar
  25. 25.
    F. Jilek and H. Hormann, Cold-insoluble globulin. III. Cyanogen bromide and plasminolysis fragments containing a label introduced by transamidation, Hoppe-Seyler’s Z. Physiol. Chem. 358:1165 (1977).Google Scholar
  26. 26.
    A.B. Robbins, J.E. Doran, A.C. Reese, A.R. Mansberger, Cold-insoluble globulin levels in operative trauma: serum depletion, wound sequestration and biological activity: an experimental and clinical study, Am. Surg. 46:663 (1980).Google Scholar
  27. 27.
    R.A.F. Clark, H.J. Winn, H.F. Dvorak, and R.P. Colvin, Fibronectin beneath reepithelializing epidermis in vivo; sources and significance, J. Invest. Dermatol. 80:265 (1983).CrossRefGoogle Scholar
  28. 28.
    R.A.F. Clark, P. DellaPelle, E. Manseau, J.M. Lanigan, H.F. Dvorak, and R.Bo Colvin, Blood vessel fibronectin increases in conjunction with endothelial cell proliferation and capillary ingrowth during wound healing, J. Invest. Dermatol. 79:269 (1982).CrossRefGoogle Scholar
  29. 29.
    J.R. Couchman, W.T. Gibson, Do Thorn, A.C. Weaver, D.A. Rees, and W.E. Parish, Fibronectin distribution in epithelial and associated tissues of the rat. Arch. Dermatol. Res, 266:295 (1979).CrossRefGoogle Scholar
  30. 30.
    W.T. Gibson, J.R. Couchman, and A.C. Weaver, Fibronectin distribution during the development of fetal rat skin, J. Invest, Dermatol, 8l:480 (1983).CrossRefGoogle Scholar
  31. 31.
    D.R. Critchley, M.A. England, J. Wakely, and R.O. Hynes, Distribution of fibronectin in the ectoderm of gastrul- ating embryos, Nature, Lond. 280:498 (1979)«.CrossRefGoogle Scholar
  32. 32.
    B.W. Mayer, E.D. Hay, and R.O. Hynes, Immunocytochemical localization of fibronectin in embryonic chick trunk and area vasculosa, Dev. Biol, 82:267 (l98l).CrossRefGoogle Scholar
  33. 33.
    J. Heasman, R.O. Hynes, A.P. Swan, V, Thomas, and C.C. Wylie, Primordial germ cells of Xenopus embryos: the role of fibronectin in their adhesion during migration, Cell 27: 437 (1981).CrossRefGoogle Scholar
  34. 34.
    J.C. Boucaut, T. Darnibere, H. Boulebache, and J.P. Thiery, Prevention of gastrulation but not neuralation by antibodies to fibronectin in amphibian embryos, Nature, Lond. 307:364 (1984).CrossRefGoogle Scholar
  35. 35.
    J.P. Thiery, J.-L. Duband, A. Delouvee, G. Tucker, H. Aoyama, T.J. Poole, and K.M. Yamada© Ontogeny of the peripheral nervous system, J. Embryol. exp. Morphol. 82:35 (1984).Google Scholar
  36. 36.
    G.A. Dunn, Contact guidance of cultured tissue cells: a survey of potentially relevant properties of the substratum, in “Cell Behaviour”, R. Bellairs, A.S.G. Curtis, G.A. Dunn, eds., Cambridge University Press, Cambridge (1982).Google Scholar
  37. 37.
    D.C. Turner, J. Lawton, P. Dollenmeier, R. Ehrismann, and M. Chiquet, Guidance of myogenic cell migration by oriented deposits of fibronectin, Dev. Biol. 95: 497(1983).CrossRefGoogle Scholar
  38. 38.
    A. Baron-Von Evercooren, H.K. Kleinman, S. Ohno, P. Marangos, I.P. Schwartz, and M.E. Dubois-Dalcq, Nerve growth factor, laminin and fibronectin promote neurite outgrowth in human fetal sensory ganglion cultures, J. Neurosci. Res. 8:179 (1982).CrossRefGoogle Scholar
  39. 39.
    R.O. Hynes and A.T. Destree, Relationships between fibronectin (LETS protein) and actin, Cell 15:875 (1977).CrossRefGoogle Scholar
  40. 40.
    V.-P. Lehto, T. Vartio, and I. Virtanen, Fibronectin remains in the cytoskeletal preparations of cultured human fibroblasts, Cell Biol. Int. Rep. 5:417 (1981).CrossRefGoogle Scholar
  41. 41.
    J.D. Aplin, R.C. Hughes, C.L. Jaffe, and N. Sharon, Reversible cross-linking of cellular components of adherent fibroblasts to fibronectin and lectin-coated substrata, Exp. Cell Res. 134:488 (1981).CrossRefGoogle Scholar
  42. 42.
    H.K. Kleinman, G.R. Martin, and P.HC Fishman, Ganglioside inhibition of fibronectin-mediated cell adhesion to collagen, Proc. Natl. Acad. Sci. U.S.A. 76:3367 (1979).CrossRefGoogle Scholar
  43. 43.
    P.J. Brown and R.L. Juliano, Admodulin: A cell surface glycoprotein specifically involved in fibronectin-mediated adhesion, J. Cell Biol. 99:16la (1984).CrossRefGoogle Scholar
  44. 44.
    T. Hasegawa, E. Hasegawa, W.-T. Chen, and K.M. Yamada, Characterization of a membrane glycoprotein complex implicated in cell adhesion to fibronectin, J. Cell Biol. 99:165a (1984).Google Scholar
  45. 45.
    R.C. Hughes, S.D.J. Pena, J. Clark, and R.R. Dourmashkin, Molecular requirements for the adhesion and spreading of hamster fibroblasts, Exp. Cell Res. 121:307 (1979).CrossRefGoogle Scholar
  46. 46.
    L. Kjellen, I. Pettersson, and M. Hook, Cell-surface heparan sulfate: an intercalated membrane proteoglycan, Proc. Nat. Acad. Sci. U.S.A. 78:5371 (1981).CrossRefGoogle Scholar
  47. 47.
    A.C. Rapraeger and M. Bernfield, Heparan sulfate proteoglycans from mouse mammary epithelial cells, J. Biol. Chem. 258: 3632 (1983).Google Scholar
  48. 48.
    L.S. Fransson, I. Carlstedt, L. Coster, and A. Malmstrom, Structure and function of cell-surface associated proteo- heparan sulphate, Eur. J. Cell Biol. 1:18 (1983).Google Scholar
  49. 49.
    A. Woods, M. Hook, L. Kjellen, C.G. Smith, and D.A. Rees, Relationship of heparan sulfate proteoglycans to the cytoskeleton and extracellular matrix of cultured fibroblasts, J. Cell Biol. 99:1743 (1984).CrossRefGoogle Scholar
  50. 50.
    A. Woods, J.R. Couchman, M. Hook, and So Johansson, Adhesion and cytoskeletal organisation of fibroblasts in response to fibronectin peptides. In Preparation.Google Scholar
  51. 51.
    M.D. Pierschbacher and E. Ruoslahti, Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule, Nature, Lond. 309:30 (1984).CrossRefGoogle Scholar
  52. 52.
    S. Johansson, Demonstration of high affinity fibronectin-receptors on rat hepatocytes in suspension, J. Biol. Chem. In Press (1985).Google Scholar
  53. 53.
    A. Garcia-Pardo, E. Pearlstein, and B. Frangione, Primary structure of human plasma fibronectin. The 29,000-dalton NHterminal domain, J. Biol. Chem. 258:12670 (1983).Google Scholar
  54. 54.
    K. Sekiguchi, S. Hakomori, M. Funahashi, I. Matsumoto, and N. Seno, Binding of fibronectin and its proteolytic fragments to glycosaminoglycans, J. Biol. Chem. 258:14359 (1983).Google Scholar
  55. 55.
    R. Timpl, H. Rohde, P.Go Robey, S.I. Rennard, J.M. Foidart, and G.R. Martin, Laminin - A glycoprotein from basement membranes, J. Biol. Chem. 254:9933 (1979).Google Scholar
  56. 56.
    D. Edgar, R. Timpl, and H. Thoenen, The heparin-binding domain of laminin is responsible for its effects on neurite outgrowth and neuronal survival, EMBO J. 3:1463 (1984).Google Scholar
  57. 57.
    R. Timpl, S. Johansson, V. van Delden, I. Oberbaumer, and M. Hook, Characterization of protease-resistant fragments of laminin mediating attachment and spreading of rat hepatocytes, J. Biol. Chem. 258:8922 (1983).Google Scholar
  58. 58.
    J. Jilek and H. Hormann, Fibronectin (cold-insoluble globulin). VI. Influence of heparin and hyaluronic acid on the binding of native collagen, Hoppe-Seyler’s Z. Physiol. Chem. 360:597 (1979).CrossRefGoogle Scholar
  59. 59.
    M.H. Ginsberg, R.G. Painter, J. Forsyth, C. Birdwell, and E.F. Plow, Thrombin increases expression of fibronectin antigen on the platelet surface, Proc. Natl. Acad. Sci. U.S.A. 77:1049 (1980).CrossRefGoogle Scholar
  60. 60.
    W.T. Gibson, J.R. Couchman, R.A. Badley, H.J. Saunders, and C.G. Smith, Fibronectin in cultured rat keratinocytes: distribution, synthesis, and relationship to cytoskeletal proteins, Eur. J. Cell Biol. 30:205 (1983).Google Scholar
  61. 61.
    D.J. Donaldson and J.T. Mahan, Fibrinogen and fibronectin as substrates for epidermal cell migration during wound closure, J. Cell Sci. 62:117 (1983).Google Scholar
  62. 62.
    J.R. Couchman and S. Blencowe, Adhesion and cell surface relationships during fibroblast and epithelial migration in vitro, in “Cell Traffic in the Developing and Adult Organism”, G. Haemmerli and P. Strauli, eds., Karger, Basel. In Press (1985).Google Scholar
  63. 63.
    A.E. Postlethwaite, J. Keski-Oja, G. Balian, and A.H. Kang, Induction of fibroblast chemotaxis by fibronectin. Localization of the chemotactic region to a 140,000- molecular weight non-gelatin-binding fragment, J. Exp. Med. 15:194 (1981).Google Scholar
  64. 64.
    H.E.J. Seppa, K.M. Yamada, S.T. Seppa, M.H. Silver, H.K. Kleinman, and E. Schiffman, The cell binding fragment of fibronectin is chemotactic for fibroblasts, Cell Biol. Int. Rep. 5:813 (1981).Google Scholar
  65. 65.
    M.B. Furie and D.B. Rifkin, Proteolytically derived fragments of human plasma fibronectin and their localization within the intact molecule, J. Biol. Chem. 255:3134 (1980).Google Scholar
  66. 66.
    I.I. Singer, D.W. Kawka, D.M. Kazazis, and R.A.F. Clark, In vivo co-distribution of fibronectin and actin fibers in granulation tissue: immunofluorescence and electron microscope studies of the fibronexus at the myofibroblast surface, J. Cell Biol. 98:2091 (1984).CrossRefGoogle Scholar
  67. 67.
    M. Kurkinen, A. Vaheri, P.J. Roberts, and S. Steinman, Sequential appearance of fibronectin and collagen in experimental granulation tissue, Lab. Invest. 43:47 (1980).Google Scholar
  68. 68.
    M.W. Lark and L.A. Culp, Multiple classes of heparan sulfate proteoglycans from fibroblast substratum adhesion sites, J. Biol. Chem. 259:6773 (1984).Google Scholar
  69. 69.
    M. Hook, L. Kjellen, S. Johansson, and J. Robinson, Cell surface glycosaminoglycans, Ann. Rev. Biochem. 53:847 (1984).CrossRefGoogle Scholar
  70. 70.
    A. Woods, J«R. Couchman, and M. Hook, Heparan sulfate proteoglycans of rat embryo fibroblastSo A hydrophobic form may link cytoskeleton and matrix components, J. Biol. Chem. Submitted.Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • John R. Couchman
    • 1
  • Anne Woods
    • 1
  1. 1.Biosciences Division Unilever Research, Colworth LaboratoryBedfordUK

Personalised recommendations