Ca2+ and CaM kinase regulate neurofilament expression

Cultured cerebellar granule neurons were used to examine the hypothesis that NMDA or KCl-dependent Ca2+ influx activates a signaling cascade mediating transcription, translation and assembly of neurofilaments. The data indicate that 25 mM KCl and 140 microM NMDA induce neurofilament protein, mRNA, and assembly in neurites, and these require Ca2+ entry through voltage-sensitive Ca2+ channels or NMDA receptors, respectively. The CaM kinase and transcriptional inhibitors, KN-62 and actinomycin D, respectively, attenuate the stimulatory effect of Ca2+. Granular neurons are a valuable model to explore the molecular basis for transcriptional regulation of neurofilament gene expression by neuronal activity.