NEURITES INDUCED BY STAUROSPORINE IN PC12 CELLS ARE RESISTANT TO COLCHICINE AND EXPRESS HIGH-LEVELS OF TAU-PROTEINS

Staurosporine, a protein kinase inhibitor, induces neurite outgrowth i n pheochromocytoma cells and, therefore, may serve as a potential prot otype for neurotropic drugs. The principal aim of the present study wa s to characterize the cytoskeletal properties of neurites induced in p heochromocytoma cells by staurosporine, in comparison to those induced by nerve growth factor, with emphasis on tubulin and tau proteins. Tw o major findings are described: a) staurosporine rapidly induces outgr owth of neurites that are resistant to colchicine treatment; and b) st aurosporine treatment causes a rapid increase in tau protein levels, w ith a time course similar to the initiation of its neurotropic effects . The following observations exclude tubulin as the cellular target fo r staurosporine action: a) the level, cellular distribution, and assem bly properties of tubulin are not affected by staurosporine treatment; and b) colchicine uptake, its binding to tubulin, and its interferenc e with tubulin polymerization are not changed by staurosporine. On the other hand, staurosporine treatment causes a transient, dose-dependen t increase in tau protein levels. This increase, which is already evid ent after 1 hr, reaches a maximum of 2 to 3 fold after 5 hr of treatme nt and declines to basal level within the next 10 to 15 hr. The rapid, transient increase of tau protein levels induced by staurosporine is reminiscent of its neurotropic properties. Here we characterize and co mpare the cytoskeletal properties of neurites induced by treatment wit h staurosporine and with nerve growth factor, and we offer a mechanist ic explanation for the rapid stabilization of staurosporine induced ne urites.