NERVE GROWTH-FACTOR STIMULATES GAP-43 EXPRESSION IN PC12 CELL CLONES INDEPENDENTLY OF NEURITE OUTGROWTH

Expression of the growth associated protein GAP-43 (B-50, F1, neuromod ulin) increases with the onset of neuronal development as seen by the growth of axons. To investigate the relationship of the signaling even ts leading to GAP-43 expression and neurite outgrowth, we examined PC1 2 clones with different phenotypes. Three clones, PC12-N09, PC12-N15, and PC12-N21, responded to NGF with increased expression of GAP-43, bu t only two clones, PC12-N15 and PC12-N21, responded with growth of neu rites. Similar increases in expression of GAP-43 were obtained when th ese clones were exposed to the phorbol ester PMA. Thus, NGF and PMA in duced GAP-43 expression in PC12-N09 cells in the absence of neurite ou tgrowth. In contrast, all three clones, were able to respond to forsko lin (FOR) by initiation of long neurites which had synaptophysin in th e growth cones, but showed only low levels of GAP-43. Combined stimula tion of PC12-N09 cells with FOR and PMA both initiated neurites and in creased expression of GAP-43 as seen in normal PC12 cells. These resul ts show that PC12-N09 cells, in response to either NGF or PMA, can exp ress GAP-43, but without neurite outgrowth, and that all the PC12 clon es were also able to respond to FOR with increased neurite outgrowth i n the presence of low levels of GAP-43. The dissociation of GAP-43 exp ression and growth of neurites observed in PC12-N09 cells suggests tha t signaling mechanisms can independently regulate GAP-43 expression an d neurite outgrowth during neuronal differentiation. (C) 1993 Wiley-Li ss, Inc.