Proteolytic regulation of neurite outgrowth from neuroblastoma cells by thrombin and protease nexin‐1

This review summarizes studies on the reciprocal regulation of neuroblastoma neurite outgrowth by thrombin and protease nexin‐1 (PN‐1). PN‐1 recently was shown to possess the same deduced amino acid sequence as the glial‐derived neurite‐promoting factor. The neurite outgrowth activity of PN‐1 depends on its ability to inhibit thrombin. Thrombin not only blocks the neurite outgrowth activity of PN‐1, but it also brings about neurite retraction in the presence of PN‐1. Thrombin also produces neurite retraction in the absence of PN‐1 and other regulatory factors. This suggests that its activity is due to a direct action on cells. The neurite retraction by thrombin depends on its proteolytic activity. It does not occur with the other serine proteases that have been tested, indicating that it is a specific effect and is not due to a general proteolytic effect that could detach neurites from the culture dish. Serum brings about neurite retraction in certain neuroblastoma cells and primary neuronal cultures; most of this activity is due to residual thrombin in the serum. Together, these results suggest that PN‐1 and thrombin (or a thrombin‐like protease) play a role in regulation of neurite outgrowth.