Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/40042
Title: Brain-derived Neurotrophic Factor Regulates the Expressionand Synaptic Delivery of -Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor Subunits in Hippocampal Neurons
Authors: Caldeira, Margarida V., Melo, Carlos V., Pereira, Daniela B., Carvalho, Ricardo, Correia, Susana S., Backos, D. S., Carvalho, Ana Luisa, Esteban, José A., Duarte, Carlos B.
Keywords: AMPA
GluR1
GluR2
GluR3
Synaptic plasticity
Brain-derived neurotrophic factor
Issue Date: 27-Apr-2007
Publisher: American Society for Biochemistry and Molecular Biology
Abstract: Brain-derived neurotrophic factor (BDNF) plays an important role in synaptic plasticity in the hippocampus, but the mechanisms involved are not fully understood. The neurotrophin couples synaptic activation to changes in gene expression underlying long term potentiation and short term plasticity. Here we show that BDNF acutely up-regulates GluR1, GluR2, and GluR3 -amino-3-hydroxy-5-methyl-4- isoxazole propionic acid (AMPA) receptor subunits in 7-day tropomyosin-related kinase in vitro cultured hippocampal neurons. The increase in GluR1 and GluR2 protein levels in developing cultures was impaired by K252a, a Trk inhibitor, and by translation (emetine and anisomycin) and transcription ( -amanitine and actinomycin D) inhibitors. Accordingly, BDNF increased the mRNA levels for GluR1 and GluR2 subunits. Biotinylation studies showed that stimulation with BDNF for 30 min selectively increased the amount of GluR1 associated with the plasma membrane, and this effect was abrogated by emetine. Under the same conditions, BDNF induced GluR1 phosphorylation on Ser-831 through activation of protein kinase C and Ca2 -calmodulin-dependent protein kinase II. Chelation of endogenous extracellular BDNF with TrkB-IgG selectively decreased GluR1 protein levels in 14-day in vitro cultures of hippocampal neurons. Moreover, BDNF promoted synaptic delivery of homomeric GluR1 AMPA receptors in cultured organotypic slices, by a mechanism independent of NMDA receptor activation. Taken together, the results indicate that BDNF up-regulates the protein levels of AMPA receptor subunits in hippocampal neurons and induces the delivery of AMPA receptors to the synapse.
Publisher version (URL): http://dx.doi.org/10.1074/jbc.M700607200
URI: http://hdl.handle.net/10261/40042
ISSN: 0021-9258
Citation: Journal of Biological Chemistry 282(17):12619-28 (2007)
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