PMID- 17337442
OWN - NLM
STAT- MEDLINE
DCOM- 20070614
LR  - 20220318
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 282
IP  - 17
DP  - 2007 Apr 27
TI  - Brain-derived neurotrophic factor regulates the expression and synaptic delivery 
      of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunits in 
      hippocampal neurons.
PG  - 12619-28
AB  - 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 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor 
      subunits in 7-day in vitro cultured hippocampal neurons. The increase in GluR1 
      and GluR2 protein levels in developing cultures was impaired by K252a, a 
      tropomyosin-related [corrected] kinase (Trk) inhibitor, and by translation 
      (emetine and anisomycin) and transcription (alpha-amanitine and actinomycin D) 
      inhibitors [corrected] 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 (alpha-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 
      Ca(2+)-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.
FAU - Caldeira, Margarida V
AU  - Caldeira MV
AD  - Center for Neuroscience and Cell Biology, Department of Zoology, University of 
      Coimbra, 3004-517 Coimbra, Portugal.
FAU - Melo, Carlos V
AU  - Melo CV
FAU - Pereira, Daniela B
AU  - Pereira DB
FAU - Carvalho, Ricardo
AU  - Carvalho R
FAU - Correia, Susana S
AU  - Correia SS
FAU - Backos, Donald S
AU  - Backos DS
FAU - Carvalho, Ana Luisa
AU  - Carvalho AL
FAU - Esteban, Jose A
AU  - Esteban JA
FAU - Duarte, Carlos B
AU  - Duarte CB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070302
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
EIN - J Biol Chem. 2007 Sep 14;282(37):27556
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cells, Cultured
MH  - Chromosome Pairing/physiology
MH  - Hippocampus/cytology/*metabolism
MH  - Immunoglobulin G/genetics/pharmacology
MH  - Neurons/cytology/*metabolism
MH  - Phosphorylation
MH  - Protein Kinase C/metabolism
MH  - Protein Processing, Post-Translational/*drug effects
MH  - Protein Transport/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/genetics
MH  - Receptors, AMPA/*biosynthesis
MH  - Recombinant Fusion Proteins/genetics/pharmacology
MH  - Up-Regulation/*drug effects/physiology
EDAT- 2007/03/06 09:00
MHDA- 2007/06/15 09:00
CRDT- 2007/03/06 09:00
PHST- 2007/03/06 09:00 [pubmed]
PHST- 2007/06/15 09:00 [medline]
PHST- 2007/03/06 09:00 [entrez]
AID - S0021-9258(18)95035-0 [pii]
AID - 10.1074/jbc.M700607200 [doi]
PST - ppublish
SO  - J Biol Chem. 2007 Apr 27;282(17):12619-28. doi: 10.1074/jbc.M700607200. Epub 2007 
      Mar 2.