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.
Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Cuong J
CJ
Bui
Carol M
CM
Beaman-Hall
Mary L
ML
Vallano
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000494:pharmacology; D016900:Neurofilament Proteins / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D011189:Potassium Chloride; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium