Cultures of dissociated neonatal mouse cerebellar cells secrete primarily tissue plasminogen activator (tPA) and to a lesser extent urokinase plasminogen activator (uPA) into the culture medium. Fibrin overlays have localized plasminogen activator to granule neurons in these cultures; furthermore, this granule cell plasminogen activator activity is blocked by an antibody to tPA. Developmental studies indicate that maximal levels of soluble plasminogen activator in the culture medium preceed the peak of fibrinolytic activity by these cultures, suggesting that secreted PA may bind back to the surface of these granule neurons. Here we show that granule cell-associated tPA can be displaced by a brief pH shock. However, incubation of these fibrinolytically inactive cultures with exogenously added mouse tPA leads to a specific binding of active tPA to granule neurons as visualized by subsequent fibrin overlay. In similar studies mouse uPA, human uPa, and human tPA fail to show fibrinolytic activity associated with the cerebellar culture, whereas mouse tPA fails to bind to cerebellar glial cell cultures. These findings suggest that granule neurons possess binding sites for tPA on their surface, where this protease can retain its functional activity and may play an important role in cell migration or other cell activities.

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Induction of tissue plasminogen activator in differentiated NG108-15 cells.

Plasminogen activators may facilitate neurite outgrowth and neuronal migration in the developing nervous system. The expression of tissue plasminogen activator by NG108-15 neuroblastoma grown under a variety of conditions has been explored. High tissue plasminogen mRNA expression correlates with growth conditions which induce morphological differentiation and neurite outgrowth; however, NG108-15 cells grown in suspension with dibutyryl-cAMP also show a high level of tissue plasminogen activator expression.

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