NMDA-mediated and self-induced bdnf exon IV transcriptions are differentially regulated in cultured cortical neurons.
Activity-dependent transcriptional up-regulation of bdnf (brain-derived neurotrophic factor) is involved in regulating many aspects of neuronal functions. The NMDA (N-methyl-D-aspartic acid)-mediated and BDNF-mediated exon IV transcription may represent mechanistically different responses, and relevant to activity-dependent changes in neurons. We found that the activities of ERK (extracellular signal regulated kinase), CaM KII/IV (calmodulin-dependent protein kinase II and IV), PI3K (phosphoinositide 3-kinase), and PLC (phospholipase C) are required for NMDA receptor-mediated bdnf exon IV transcription in cultured cortical neurons. In contrast, the BDNF-induced and TrkB-dependent exon IV transcription was regulated by ERK and CaM KII/IV, but not by PI3K and PLC. While ERK and CaM KII/IV are separate signaling pathways in BDNF-stimulated neurons, CaM KII/IV appeared to regulate exon IV transcription through ERK in NMDA-stimulated neurons. Similarly, the PI3K and PLC signaling pathways converged on ERK in NMDA- but not BDNF-stimulated neurons. Our results implicate that the NMDA-induced and the self-maintenance of bdnf transcription are differentially regulated.
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, 48824, USA.
Fei
F
Zheng
Hongbing
H
Wang
D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005091:Exons / Q000187:drug effects / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D018690:Excitatory Amino Acid Agonists; D016202:N-Methylaspartate; D019869:Phosphatidylinositol 3-Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases; D010738:Type C Phospholipases