DOMINANT-NEGATIVE ATF1 BLOCKS CYCLIC AMP-INDUCED NEURITE OUTGROWTH INPC12D CELLS

Extension of the neuronal process is a crucial step for establishment of the neuronal network. As CREB preferentially forms heterodimers wit h ATF1 in PC12D cells, we examined the roles of the CREB/ATF1 heterodi mer on cyclic AMP (cAMP)-induced neurite extension, using originally c onstructed ATF1RL, which has a paint mutation at the DNA binding domai n of ATF1. Transient expression of ATF1RL suppressed the protein kinas e A/ CREB-induced expression of the CRE reporter gene as expected, Tre atment with forskolin elicited a relatively poor mRNA induction for im mediate early genes in PC12D-ATF1RL cells, a PC12D cell line stably ex pressing ATF1RL, in comparison with the parental PC12D cells. Furtherm ore, the PC12D-ATF1RL cells were proved to be defective at cAMP-induce d neurite outgrowth. In contrast, both the gene expression and the dif ferentiation after nerve growth factor treatment noted in PC12D-ATF1RL cells were at the same levels as those in the parental cells. These d ata provide us the first evidence that links CREB/ATF1 to the cAMP-ind uced differentiation of PC12 cells.