Journal of Biological Chemistry · 2003 · 66 citations · 27 references
The neurotrophin brain-derived neurotrophic factor (BDNF), via activation of its receptor, tyrosine receptor kinase B (trkB), regulates a wide variety of cellular processes in the nervous system, including neuron survival and synaptic plasticity. Although the expression of BDNF is known to be Ca 2 -dependent, the regulation of trkB expression has not been extensively studied. Here we report that depolarization of cultured mouse cortical neurons increased the expression of the full-length, catalytically active isoform of trkB without affecting expression of the truncated isoform. This increase in protein expression was accompanied by increased levels of transcripts encoding full-length, but not truncated, trkB. Depolarization also regulated transcription of the gene, TRKB, via entry of Ca 2 through voltage-gated Ca 2 channels and subsequent activation of Ca 2 -responsive elements in the two TRKB promoters. Using transient transfection of neurons with TRKB promoterluciferase constructs, we found that Ca 2 inhibited the upstream promoter P1 but activated the downstream promoter P2. Ca 2 -dependent stimulation of TRKB expression requires two adjacent, non-identical CRE sites located within P2. The coordinated regulation of BDNF and trkB by Ca 2 may play a role in activity-dependent survival and synaptic plasticity by enhancing BDNF signaling in electrically active neurons.
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