遺伝子発現屋の脳神経科学

抄録

  My former research focused on silk fibroin gene transcription. The in vivo transcription initiation site of the fibroin gene, which is similar to the site corresponding to the 5′-terminal of mature fibroin mRNA, was determined. By developing a cell-free transcription system prepared from silk glands, it was found that the upstream region of the fibroin gene is responsible for efficient transcription initiation, which has enhancer-like features. More recent research has switched my focus to cellular neurobiology to understand the molecular mechanisms of long-term memory at the level of gene expression in terms of cell differentiation. I first developed an experimental system to analyze promoter activity in primary cultured neuronal cells. Particularly focusing on the transcription regulation of the brain-derived neurotrophic factor (BDNF) gene (Bdnf), I found that the interaction of the cAMP response element-binding protein (CREB) with the CRE sequence is important for the activity-dependent activation of the Bdnf promoter. In addition, this activity-dependent transcriptional regulation occurs in cultured neurons stimulated with excitatory GABAergic inputs, which plays a critical role in promoting the step of neuronal differentiation. Finally, I found that stimulation of the G-protein coupled receptor (GPCR) effectively activates Bdnf promoter IV through selective activation of the calcineurin pathway, irrespective of the type of GPCR if the protein kinase A or C pathway is activated. This induction mechanism appears important to understand intracellular mechanisms evoked via simultaneous neurotransmission of excitatory and modulatory inputs into neurons of the brain.