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Closed Access item 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.
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|
|Publisher:||American Society for Biochemistry and Molecular Biology|
|Citation:||Journal of Biological Chemistry 282(17):12619-28 (2007)|
|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
|Publisher version (URL):||http://dx.doi.org/10.1074/jbc.M700607200|
|Appears in Collections:||(CBM) Artículos|
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