PMID- 12900419 OWN - NLM STAT- MEDLINE DCOM- 20031203 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 278 IP - 42 DP - 2003 Oct 17 TI - Ca(2+)-dependent regulation of TrkB expression in neurons. PG - 40744-8 AB - 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. FAU - Kingsbury, Tami J AU - Kingsbury TJ AD - Departments of Physiology and Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. tking001@umaryland.edu FAU - Murray, Peter D AU - Murray PD FAU - Bambrick, Linda L AU - Bambrick LL FAU - Krueger, Bruce K AU - Krueger BK LA - eng SI - GENBANK/AY307416 GR - 2T32GM08181/GM/NIGMS NIH HHS/United States GR - 5T32NS07375/NS/NINDS NIH HHS/United States GR - AG10686/AG/NIA NIH HHS/United States GR - NS40492/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. DEP - 20030804 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - E0399OZS9N (Cyclic AMP) RN - EC 1.13.12.- (Luciferases) RN - EC 2.7.10.1 (Receptor, trkB) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Binding Sites MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Calcium/*metabolism MH - Cells, Cultured MH - Cyclic AMP/metabolism MH - Down-Regulation MH - *Gene Expression Regulation MH - Luciferases/metabolism MH - Mice MH - Models, Genetic MH - Molecular Sequence Data MH - Neurons/*metabolism MH - Plasmids/metabolism MH - Promoter Regions, Genetic MH - RNA, Messenger/metabolism MH - Receptor, trkB/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction MH - Time Factors MH - Transfection EDAT- 2003/08/06 05:00 MHDA- 2003/12/04 05:00 CRDT- 2003/08/06 05:00 PHST- 2003/08/06 05:00 [pubmed] PHST- 2003/12/04 05:00 [medline] PHST- 2003/08/06 05:00 [entrez] AID - S0021-9258(20)82864-6 [pii] AID - 10.1074/jbc.M303082200 [doi] PST - ppublish SO - J Biol Chem. 2003 Oct 17;278(42):40744-8. doi: 10.1074/jbc.M303082200. Epub 2003 Aug 4.