PMID- 17045972
OWN - NLM
STAT- MEDLINE
DCOM- 20070212
LR  - 20120605
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1121
IP  - 1
DP  - 2006 Nov 22
TI  - Brain-derived neurotrophic factor rapidly increases NMDA receptor channel 
      activity through Fyn-mediated phosphorylation.
PG  - 22-34
AB  - Brain-derived neurotrophic factor (BDNF) is a potent modulator of hippocampal 
      synaptic plasticity. Previously, we found that one of the targets of BDNF 
      modulation is NR2B-containing NMDA receptors. Furthermore, exposure to the 
      trophin rapidly increases NMDA receptor activity and enhances tyrosine 
      phosphorylation of NR2B in cortical and hippocampal postsynaptic densities 
      (PSDs), potentially linking receptor phosphorylation to synaptic plasticity. To 
      define the specific NR2B residue(s) regulated by BDNF, we focused on tyrosine 
      1472, phosphorylation of which increases after LTP. BDNF rapidly increased 
      phosphorylation in cortical PSDs. The tyrosine kinase Fyn is critical since 
      BDNF-dependent phosphorylation was abolished in Fyn knockout mice. Single-channel 
      patch clamp recordings showed that Fyn is required for the increase in NMDA 
      receptor activity elicited by BDNF. Collectively, our results suggest that BDNF 
      enhances phosphorylation of NR2B tyrosine 1472 through activation of Fyn, leading 
      to alteration of NMDA receptor activity and increased synaptic transmission.
FAU - Xu, Fei
AU  - Xu F
AD  - Department of Neuroscience and Cell Biology, University of Medicine and Dentistry 
      of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
FAU - Plummer, Mark R
AU  - Plummer MR
FAU - Len, Guo-Wei
AU  - Len GW
FAU - Nakazawa, Takanobu
AU  - Nakazawa T
FAU - Yamamoto, Tadashi
AU  - Yamamoto T
FAU - Black, Ira B
AU  - Black IB
FAU - Wu, Kuo
AU  - Wu K
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20061013
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.7.10.2 (Fyn protein, mouse)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Culture Techniques
MH  - Cerebral Cortex/drug effects/physiology
MH  - Hippocampus/cytology/embryology/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/drug effects/*physiology
MH  - Phosphorylation
MH  - Phosphotyrosine/metabolism
MH  - Proto-Oncogene Proteins c-fyn/deficiency/genetics/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/drug effects/*physiology
EDAT- 2006/10/19 09:00
MHDA- 2007/02/13 09:00
CRDT- 2006/10/19 09:00
PHST- 2006/03/17 00:00 [received]
PHST- 2006/07/13 00:00 [revised]
PHST- 2006/08/27 00:00 [accepted]
PHST- 2006/10/19 09:00 [pubmed]
PHST- 2007/02/13 09:00 [medline]
PHST- 2006/10/19 09:00 [entrez]
AID - S0006-8993(06)02634-5 [pii]
AID - 10.1016/j.brainres.2006.08.129 [doi]
PST - ppublish
SO  - Brain Res. 2006 Nov 22;1121(1):22-34. doi: 10.1016/j.brainres.2006.08.129. Epub 
      2006 Oct 13.