Interaction of Plasminogen Activators with the Neuronal Surface

  • Randall N. Pittman
  • Ann Repka
  • Jeff H. Ware
  • Ann Marie LaRosa
Part of the NATO ASI Series book series (NSSA, volume 191)


Extensive structural and cellular changes are conspicuous features of the developing organism. The mechanisms underlying these changes are in general unknown and few of the molecules responsible for dynamic events such as morphogenesis and differentiation have been identified. Proteolytic activity is an ideal mechanism for producing many of the changes characteristic of the developing organism. Proteases have been implicated in a number of prominent developmental events including trophoblast implantation,1,2 pattern formation,3 migration,4 cell proliferation,5–7 and differentiation.8 Proteases present in the nervous system have been implicated in a number of developmental events including glial proliferation,9,10 neural crest and granule cell migration,11–13 and neurite outgrowth.14–20


PC12 Cell Plasminogen Activator Serine Protease Neurite Outgrowth Growth Cone 
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.
    S. Strickland, E. Reich, and M.I. Sherman, Plasminogen activator in early embryogenesis:enzyme production by trophoblast and parietal endoderm. Cell 9: 231–240 (1976).CrossRefPubMedGoogle Scholar
  2. 2.
    R.H. Glass, J. Aggeler, A. Spindle, RA. Pendersen, and Z. Werb, Degradation of extracellular matrix by mouse trophoblast outgrowth: a model for implantation. J. Cell BioL 96: 1108–1116 (1983).CrossRefPubMedGoogle Scholar
  3. 3.
    R. DeLotto, and P. Spierer, A gene required for the specification of dorsal-ventral pattern in Drosophila appears to encode a serine protease. Nature 323: 688–692 (1986).CrossRefPubMedGoogle Scholar
  4. 4.
    J.E. Valinsky, E. Reich, and N.M. Le Douarin, Plamsinogen activator in the bursa of Fabricius. Correlations with morphogenetic remodeling and cell migrations. Cell 25: 471–476 (1981).CrossRefPubMedGoogle Scholar
  5. 5.
    D.H. Carney, Perspectives on the cellular and biochemical effects of thrombin interaction with surface receptors and substrate molecules. In Proteases in Biological Control and Biotechnology, D.D. Cunningham and G.L. Long, eds., pp. 277–282, Alan R. Liss, New York (1987).Google Scholar
  6. 6.
    D.H. Carney, and D.D. Cunningham, Initiation of chick cell division by trypsin action at the cell surface. Nature 268: 602–606 (1977).CrossRefPubMedGoogle Scholar
  7. 7.
    L.B. Chen, and J.M. Buchanan, Mitogenic activity of blood components. I. Thrombin and prothrombin. Proc. NatL Acad. Sci. USA 72: 131–135 (1975).CrossRefPubMedGoogle Scholar
  8. 8.
    G. Ortolan, E. Patricolo, and C. Mansueto, Trypsin-induced cell surface changes in ascidan embryonic cells. Exp. Cell Res. 122: 137–147 (1979).CrossRefGoogle Scholar
  9. 9.
    N. Kalderon, Schwann cell proliferation and localized proteolysis: Expression of plasminogen-activator activity predominates in the proliferating cell populations. Proc. NatL Acad. Sci., USA 81: 72167220 (1984).Google Scholar
  10. 10.
    G. Moonen, M.-P. Grau-Wagemans, I. Selak, Ph.P. Lefebvre, B. Rogister, J.D. Vassalli, and D. Belin, Plasminogen activator is a mitogen for astrocytes in developing cerebellum. Dev. Br. Res. 20: 4148 (1985).CrossRefGoogle Scholar
  11. 11.
    G. Moonen, M.P. Grau-Wagemans, and I. Selak, Plasminogen activator-plasmin system and neuronal migration. Nature 298: 753–755 (1982).Google Scholar
  12. 12.
    J.E. Valinsky, and N.M. LeDouarin, The production of plasminogen activator by migrating cephalic neural crest cells. EMBO J. 4: 1403–1406 (1985).Google Scholar
  13. 13.
    G. Grossman, J.P. Quigley, and J.E. Valinsky, An antibody with anti-catylitic activity against chicken plasminogen activator inhibits neural crest cell migration in vitro. J. Cell Biol. Abstr. 105: 1256 (1987).Google Scholar
  14. 14.
    D. Monard, E. Miday, A. Limat, and F. Solomon, Inhibition of protease activity can lead to neurite extension in neuroblastoma cells. Prog. Brain Res. 58: 359–64 (1983).CrossRefPubMedGoogle Scholar
  15. 15.
    J. Guenther, N. Hanspeter, and D. Monard, A glia-derived neurite promoting factor with protease inhibitory activity. EMBO J. 4: 1963–1966 (1985).Google Scholar
  16. 16.
    R.L. Hawkins, and N.W. Seeds, Effect of proteases and their inhibitors on neurite outgrowth from neonatal mouse sensory ganglia in culture. Br. Res. 398: 63–70 (1986).CrossRefGoogle Scholar
  17. 17.
    R.N. Pittman, and P.H. Patterson, Characterization of an inhibitor of neuronal plasminogen activator released by heart cells. J. Neurosci. 7: 2664–2673 (1987).PubMedGoogle Scholar
  18. 18.
    A.D. Zum, H. Nick, and D. Monard, A glia-derived nexin promotes neurite outgrowth in cultured chick sympathetic neurons. Dev. Neurosci. 10: 17–24 (1988).CrossRefGoogle Scholar
  19. 19.
    D. Gurwitz, and D.D. Cunningham, Thrombin modulates and reverses neuroblastoma neurite outgrowth. Proc. NatL Acad. Sci. U.SA. 85: 3440–3444 (1988).CrossRefGoogle Scholar
  20. 20.
    R.N. Pittman, J.K. Ivins, and H.M. Buettner, Neuronal plamsinogen activators:Cell surface binding sites and involvement in neurite outgrowth. J. Neurosci. 9: (1989a).Google Scholar
  21. 21.
    A. Krystosek, and N.W. Seeds, Plasminogen activator release at the neuronal growth cone. Science 213: 1532–1534 (1981).CrossRefPubMedGoogle Scholar
  22. 22.
    A. Krystosek, and N.W. Seeds, Peripheral neurons and Schwann cells secrete plasminogen activator. J. Cell BioL 98: 773–776 (1984).CrossRefPubMedGoogle Scholar
  23. 23.
    R.N. Pittman, Release of plasminogen activator and a calcium-dependent metalloprotease from cultured sympathetic and sensory neurons. Dev. BioL 110: 91–101 (1985).CrossRefPubMedGoogle Scholar
  24. 24.
    R.N. Pittman, and A. G. Williams, Neurite penetration into collagen gels requires Cat+-dependent metalloproteinase activity. Dev. Neurosci. 11: 41–51 (1989).CrossRefPubMedGoogle Scholar
  25. 25.
    R.W. Scott, and J.B. Baker, Purification of human protease nexin. J. BioL Chem. 258: 10439–10444 (1983).PubMedGoogle Scholar
  26. 26.
    D.L. Eaton, and J.B. Baker, Evidence that a variety of cultured cells secrete protease nexin and produce a distinct cytoplasmic serine protease-binding factor. J. CelL Physiol. 117: 175–182 (1983).CrossRefPubMedGoogle Scholar
  27. 27.
    LA. Erickson, C.M. Kekman, and D.J. Loskutoff, The primary plasminogen-activator inhibitors in endothelial cells, platelets, serum, and plasma are immunologically related. Proc. Natl. Acad. Sci. USA 82: 8710–8714 (1985).CrossRefPubMedGoogle Scholar
  28. 28.
    S. Gloor, K. Odink, J. Guenther, H. Nick, and D. Monard, A glia-derived neurite promoting factor with protease inhibitory activity belongs to the protease nexins. Cell 47: 687–693 (1986).CrossRefPubMedGoogle Scholar
  29. 29.
    D. Monard, Cell-derived proteases and protease inhibitors as regulators of neurite outgrowth. Trends Neurosci. 11: 541–544 (1988).CrossRefPubMedGoogle Scholar
  30. 30.
    K. Dan¢, P.A. Andreasen, J. Gryindahl-Hansen, B. Kristensen, L.S. Nielsen, and L. Skriver, Plasminogen activators, tissue degradation and cancer. Adv. Cancer Res. 44: 146–239 (1985).Google Scholar
  31. 31.
    O. Saksela, and D.B. Rifkin, Cell-associated plasminogen activation: Regulation and physiological functions. Ann. Rev. Cell BioL 4: 93–126 (1988).CrossRefPubMedGoogle Scholar
  32. 32.
    J. Pöllänen, O. Saksela, E.-M. Salonen, P. Andreasen, L. Nielsen, K. Dan¢, and A. Vaheri, Distinct localizations of urokinase-type plasminogen activator and its type 1 inhibitor under cultured human fibroblasts and sarcoma cells. J. Cell Biol. 104: 1085–1096 (1987).Google Scholar
  33. 33.
    J. Pöllänen, K. Hedman, L.S. Nielsen, K. Dank, and A. Vaheri, Ultrastructural localization of plasma membrane-associated urokinase-type plasminogen activator at focal contacts. J. Cell BioL 106: 8795 (1988).CrossRefGoogle Scholar
  34. 34.
    CA. Hebert, and J.B. • Baker, Linkage of extracellular plasminogen activator to the fibroblast cytoskeleton: Colocalization of cell surface urokinase with vinculin. J. Cell Bid. 106: 1241–1247 (1988).CrossRefGoogle Scholar
  35. 35.
    Z. Werb, C. Mainardi, CA. Vater, and E.D. Harris, Endogenous activation of latent collagenase by rheumatoid synovial cells. Evidence for a role of plasminogen activator. New Engl. J. Med. 296: 1017–1023 (1977).CrossRefPubMedGoogle Scholar
  36. 36.
    P. Mignatti, E. Robbins, and D.B. Rifkin, Tumor invasion through the human amniotic membrane: Requirement for a proteinase cascade. Cell 47: 487–498 (1986).CrossRefPubMedGoogle Scholar
  37. 37.
    M.J. Katz, How straight do axons grow? J. Neurosci. 5: 589–595 (1985).PubMedGoogle Scholar
  38. 38.
    V. Argiro, M.B. Bunge, and M.I. Johnson, Correlation between growth form and movement and their dependence on neuronal age. J. Neurosci 4: 3051–3062 (1984).PubMedGoogle Scholar
  39. 39.
    D. Bray, and P.J. Hollenbeck, Growth cone motility and guidance. Ann. Rev. Cell Bid. 4: 43–62 (1988).CrossRefGoogle Scholar
  40. 40.
    LA. Greene, and A. S. Tischler, Establishment of a noradrenergic clonal cell line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc. NatL Acad. Sci. USA 73: 2424–2428 (1976).CrossRefPubMedGoogle Scholar
  41. 41.
    R.N. Pittman, P. Vos, J.K. Ivins, H.M. Buettner, and A. Repka, Proteases and inhibitors in the developing nervous system. In: Assembly of the Nervous System, L. Landmesser, ed. Alan R. Liss, Inc. New York, 109–128 (1989b).Google Scholar
  42. 42.
    G. Danglot, D. Vinson, and F. Chapeville, Qualitative and quantitative distribution of plasminogen activators in organs from healthy adult mice. FEBS Lett 194: 96–100 (1986).CrossRefPubMedGoogle Scholar
  43. 43.
    P. Kristensen, J.S. Nielsen, J. Gr¢ndahl-Hansen, P.B. Andresen, L.-I. Larsson, and K. Dan$, Immunocytochemical demonstration of tissue-type plasminogen activator in endocrine cells of the rat pituitary gland. J. Cell BioL 101: 305–311 (1985).CrossRefPubMedGoogle Scholar
  44. 44.
    P. Kristensen, J.S. Nielsen, L.-I. Larsson, and K. DanS, Tissue-type plasminogen activator in somatostatin cells of rat pancreas and hypothalamus. Endocrinology 121: 2238–2244 (1987).CrossRefPubMedGoogle Scholar
  45. 45.
    M.B. Clarke, and L.D. Snellinger, Schwann cells release both plasminogen activator and a plasminogen activator inhibitor. J. Cell BioL Abstr. 4143 (1988).Google Scholar
  46. 46.
    S. Verrall, and N.W. Seeds, Tissue plasminogen activator binding to mouse cerebellar granule neurons. J. Neurosci. Res. 21: 420–425 (1988).CrossRefPubMedGoogle Scholar
  47. 47.
    R.N. Pittman, Cell surface binding sites for plasminogen activators. Soc. Neurosi. Abstr. 14: 240. 9 (1988).Google Scholar
  48. 48.
    T. Whitford, and J.M. Levine, Secretion of tissue type plasminogen activator during neuronal differentiation of an embryonal carcinoma cell line. Soc. Neurosci. Abstr. 13: 892 (1987).Google Scholar
  49. 49.
    LA. Greene, and A.S. Tischler, PC12 pheochromocytoma cultures in neurobiological research. Adv. CelL NeurobioL 3: 373–414 (1982).Google Scholar
  50. 50.
    E.L. Wilson, and G.E. Francis, Differentiation-linked secretion of urokinase and tissue plasminogen activator by normal human hemopoietic cells. J. Exp. Med. 165: 1609–1623 (1987).CrossRefPubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Randall N. Pittman
    • 1
  • Ann Repka
    • 1
  • Jeff H. Ware
    • 1
  • Ann Marie LaRosa
    • 1
  1. 1.Department of Pharmacology 6084 School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations