Regulation of neuronal migration and neuritogenesis by distinct surface proteases. Relative contribution of plasmin and a thrombin-like protease.

The relative contribution of two neuronal surface proteases, plasmin and a protease with thrombin-like specificity, on NB2a/dl neuroblastoma migration and neuritogenesis were examined. Exogenous plasmin induced cell body rounding and increased cell migration, but did not prevent or reverse neurite outgrowth. Inhibition of endogenous plasmin by its specific inhibitor, aprotinin, suppressed migration but did not induce neuritogenesis. Removal or inhibition of the thrombin-like protease by serum deprivation or hirudin addition, respectively, induced neurite outgrowth, as shown in our previous studies, but did not suppress migration. By contrast, trypsin induced simultaneous cell rounding and neurite retraction. These findings indicated that plasmin may regulate cell migration, while the thrombin-like protease may regulate facets of neurite outgrowth. Although unable to induce de novo neuritogenesis, plasmin inhibition potentiated the otherwise transient neurites induced by simultaneous inhibition of the thrombin-like protease. Since cultured neuronal cells migrate primarily in the direction of newly elaborated neurites, this finding is interpreted to indicate that cessation of neuronal migration by plasmin inhibition enhances net neurite outgrowth by inhibition of the putative thrombin-like protease.