PMID- 17515902
OWN - NLM
STAT- MEDLINE
DCOM- 20071002
LR  - 20220408
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 10
IP  - 6
DP  - 2007 Jun
TI  - BDNF induces transport of PSD-95 to dendrites through PI3K-AKT signaling after 
      NMDA receptor activation.
PG  - 702-11
AB  - The N-methyl-D-aspartate receptor (NMDAR), brain-derived neurotrophic factor 
      (BDNF), postsynaptic density protein 95 (PSD-95) and phosphatidylinositol 
      3-kinase (PI3K) have all been implicated in long-term potentiation. Here we show 
      that these molecules are involved in a single pathway for synaptic potentiation. 
      In visual cortical neurons in young rodents, the neurotrophin receptor TrkB is 
      associated with PSD-95. When BDNF is applied to cultured visual cortical neurons, 
      PSD-95-labeled synaptic puncta enlarge, and fluorescent recovery after 
      photobleaching (FRAP) reveals increased delivery of green fluorescent 
      protein-tagged PSD-95 to the dendrites. The recovery of fluorescence requires 
      TrkB, signaling through PI3K and the serine-threonine kinase Akt, and an intact 
      Golgi apparatus. Stimulation of NMDARs mimics the PSD-95 trafficking that is 
      induced by BDNF but requires active BDNF and PI3K. Furthermore, local dendritic 
      contact with a BDNF-coated microsphere induces PSD-95 FRAP throughout the 
      dendrites of the stimulated neuron, suggesting that this mechanism induces rapid 
      neuron-wide synaptic increases in PSD-95 and refinement whenever a few robust 
      inputs activate the NMDAR-BDNF-PI3K pathway.
FAU - Yoshii, Akira
AU  - Yoshii A
AD  - Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts 
      Avenue, Cambridge, Massachusetts 02139-4307, USA. ayoshii@mit.edu
FAU - Constantine-Paton, Martha
AU  - Constantine-Paton M
LA  - eng
GR  - R01EY006039/EY/NEI NIH HHS/United States
GR  - R01EY014074/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070521
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, mouse)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.4.8 (Guanylate Kinases)
RN  - SML2Y3J35T (Colchicine)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Colchicine/pharmacology
MH  - Dendrites/*drug effects/metabolism
MH  - Disks Large Homolog 4 Protein
MH  - Drug Interactions
MH  - Enzyme Inhibitors/pharmacology
MH  - Excitatory Amino Acid Agonists/pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Glycine/pharmacology
MH  - Guanylate Kinases
MH  - Immunoprecipitation
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Membrane Proteins/*metabolism
MH  - Mice
MH  - Neurons/cytology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/*physiology
MH  - Signal Transduction/*drug effects
MH  - Transfection/methods
EDAT- 2007/05/23 09:00
MHDA- 2007/10/03 09:00
CRDT- 2007/05/23 09:00
PHST- 2006/12/20 00:00 [received]
PHST- 2007/03/30 00:00 [accepted]
PHST- 2007/05/23 09:00 [pubmed]
PHST- 2007/10/03 09:00 [medline]
PHST- 2007/05/23 09:00 [entrez]
AID - nn1903 [pii]
AID - 10.1038/nn1903 [doi]
PST - ppublish
SO  - Nat Neurosci. 2007 Jun;10(6):702-11. doi: 10.1038/nn1903. Epub 2007 May 21.