Ca(2+)-dependent regulation of TrkB expression in neurons.
نویسندگان
چکیده
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 Ca2+-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 Ca2+ through voltage-gated Ca2+ channels and subsequent activation of Ca2+-responsive elements in the two TRKB promoters. Using transient transfection of neurons with TRKB promoter-luciferase constructs, we found that Ca2+ inhibited the upstream promoter P1 but activated the downstream promoter P2. Ca2+-dependent stimulation of TRKB expression requires two adjacent, non-identical CRE sites located within P2. The coordinated regulation of BDNF and trkB by Ca2+ may play a role in activity-dependent survival and synaptic plasticity by enhancing BDNF signaling in electrically active neurons.
منابع مشابه
Ca -dependent Regulation of TrkB Expression in Neurons*
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 -dependent, the regulation of trkB expression has not been extensively studied. Here we report that ...
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Brain-derived neurotrophic factor (BDNF) is known to be crucial for the development of peripheral vestibular neurons. However, the maturation profile of the BDNF signal transducing receptor, tyrosine kinase B (TrkB) in functionally activated otolith-related vestibular nuclear neurons of postnatal rats remains unexplored. In the present study, conscious Sprague-Dawley rats (P4 to adult) were sub...
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ورودعنوان ژورنال:
- The Journal of biological chemistry
دوره 278 42 شماره
صفحات -
تاریخ انتشار 2003