(A) Site-directed mutations of NRF-1 binding sites on Kif17 promoter resulted in a significant reduction in luciferase activity as compared to the wild type (wt). KCl depolarization increased promoter activity in the wild type but not in the mutated Kif17 (NRF-1A mut and NRF-1B mut sites). (Group means were analyzed for overall statistical significance using the Student’s t-test and ANOVA, N = 6 for each construct). *, P < 0.05, as compared to Kif17 wild type. # = P < 0.05 as compared to Kif17 wt with KCl depolarization. (B) Data from real time quantitative PCR indicate that NRF-1, Kif17, Kif1a, Grin1, and Grin2b gene expression in neurons were increased by KCl depolarization as compared to controls. NRF-1 silencing with shRNA prevented the up-regulation of NRF-1, Kif17, Grin1, and Grin2b mRNAs by KCl, whereas Kif1a was not affected. Values represent mean ± S.E.M of combined data from 3 independent experiments. * P < 0.05, ** P < 0.01 versus controls. All # P values were compared to 20 mM KCl-treated samples (# P < 0.05). (C) Western blot reveals increased protein levels for both KIF17 and KIF1A following KCl depolarization as compared to controls. NRF-1 silencing with shRNA prevented the KCl-induced up-regulation of KIF17 protein levels, whereas those of KIF1A were not affected. * P < 0.01 versus controls. β-Actin served as a loading control.